Caution:Patient-specific preoperative preparations combined with procedure-specific 5-aminolevulinic acid may lead to critical events.

5-Aminolevulinic acid (5-ALA) is orally administered 2-4 hours before surgery to identify tumor location. Hypotension is sometimes observed after 5-ALA administration. Case reoprtWe present a case of a patient with 5-ALA-induced hypotension that resulted in the development of cerebral infarction. An 83-year-old man with a bladder tumor was scheduled for photodynamic diagnosis-assisted transurethral resection of bladder tumor (PDD-TURBT) and right radical nephroureterectomy. 5-ALA was orally administered and his ordinary antihypertensive and antianginal agents were also administered an hour after 5-ALA administration. Following this, his blood pressure dropped, and he developed muscle weakness and paralysis in his left upper extremity. Magnetic resonance imaging showed evidence of cerebral infarction. ConclusionsWe cannot conclude definitively that our patient's cerebral infarction was solely caused by 5-ALA-induced hypotension because hypotension under these circumstances is not rare. We consider that additional factors, such as patient-specific doses of antihypertensive and antianginal agents may have played a role in the development of his cerebral infarction.

Physiotherapy management focusing on proprioceptive impairment in a patient with gait and balance impairments following stroke: A case report.

BACKGROUND: Proprioceptive impairment contributes to gait and balance impairments in patients with stroke. Diagnosis functional impairments and evaluation treatment efficacy require quantitative proprioception assessment. However, proprioception assessment has remained limited to ordinal scale measurement, with a lack of ratio scale measurements. PURPOSE: This case report describes a physiotherapy management program focusing on proprioceptive impairment in patients with stroke using quantitative tests such as Threshold to Detect Passive Motion (TDPM) and Joint Position Sense (JPS). CASE DESCRIPTION: A63-year-old male patient with an acute pontine lacunar infarction was admitted to our hospital. His muscle strength, selective movement, and trunk activity were preserved. However, the Berg Balance Scale (BBS) and Gait Assessment andIntervention Tool (GAIT) score were 42 and 9 points, observing balance impairment and the buckling knee pattern with hip ataxia during gait. Based on these, TDPM and JPS using image capture were performed. In physiotherapeuticdiagnosis, proprioceptive impairments in the hip and knee joints were the primary functional impairments related to balance and gait. To address these proprioceptive impairments, a 13-day treatment protocol incorporating transcutaneous electrical nerve stimulation (intensity: sensory threshold, frequency: 100 Hz) targeting the quadriceps femoris was performed. OUTCOMES: The patient was discharged after achieving independent ambulation and improvement in BBS (56 points) and GAIT (2 points) scores, exceeding the minimum clinically important difference. Recovery of proprioceptive impairment corresponded withimproved balance and gait ability. CONCLUSION: Quantitatively evaluating proprioceptive impairments may provide novel rehabilitation for patients with stroke who have proprioceptive impairments and contribute to clinical decision-making.

Transferrin Biosynthesized in the Brain Is a Novel Biomarker for Alzheimer's Disease.

Glycosylation is a cell type-specific post-translational modification that can be used for biomarker identification in various diseases. Aim of this study is to explore glycan-biomarkers on transferrin (Tf) for Alzheimer's disease (AD) in cerebrospinal fluid (CSF). Glycan structures of CSF Tf were analyzed by ultra-performance liquid chromatography followed by mass spectrometry. We found that a unique mannosylated-glycan is carried by a Tf isoform in CSF (Man-Tf). The cerebral cortex contained Man-Tf as a major isofom, suggesting that CSF Man-Tf is, at least partly, derived from the cortex. Man-Tf levels were analyzed in CSF of patients with neurological diseases. Concentrations of Man-Tf were significantly increased in AD and mild cognitive impairment (MCI) comparing with other neurological diseases, and the levels correlated well with those of phosphorylated-tau (p-tau), a representative AD marker. Consistent with the observation, p-tau and Tf were co-expressed in hippocampal neurons of AD, leading to the notion that a combined p-tau and Man-Tf measure could be a biomarker for AD. Indeed, levels of p-tau x Man-Tf showed high diagnostic accuracy for MCI and AD; 84% sensitivities and 90% specificities for MCI and 94% sensitivities and 89% specificities for AD. Thus Man-Tf could be a new biomarker for AD.

Evaluation of blood-brain barrier function by quotient alpha2 macroglobulin and its relationship with interleukin-6 and complement component 3 levels in neuropsychiatric systemic lupus erythematosus.

Although quotient of alpha2 macroglobulin (Qα2MG) was previously reported to be useful for the evaluation of blood-brain barrier (BBB) function, it is not commonly used. We therefore evaluated BBB function among the various subsets of neuropsychiatric systemic lupus erythematosus (NPSLE) using quotient Q α2MG. Furthermore, we determined the correlation between Q α2MG and cerebrospinal (CSF) interleukin (IL)-6 level and quotient complement component 3 (Q C3). To determine intrathecal production of C3, the C3 index (Q C3/Q α2MG) was also calculated. Fifty-six patients with SLE were included in this study. Of these, 48 were diagnosed with NPSLE, consisting of 30 diffuse NPSLE patients (acute confusional state (ACS): n = 14, non-ACS: n = 16) and 18 patients with focal NPSLE. CSF IL-6 concentration, and paired serum and CSF levels of α2MG and C3, were measured by enzyme-linked immuno solvent assay (ELISA). The Q α2MG, Q C3, and C3 index were then calculated. Q α2MG, Q C3, and IL-6 concentrations in the CSF were significantly elevated in NPSLE compared with non-NPSLE. Among the subsets of NPSLE, significant increases in Q α2MG, CSF IL-6, and Q C3 were observed in ACS compared with non-ACS or focal NPSLE. There was a positive correlation between CSF IL-6 level and Q α2MG, as well as between Q C3 and Q α2MG, in diffuse NPSLE. There were no significant differences in C3 index between NPSLE and non-NPSLE, as well as among the subgroups of NPSLE. Our study suggests that BBB disruption is present in ACS, and elevated levels of IL-6 and C3 in CSF in diffuse NPSLE, especially in ACS, might result from their entry to the CSF from the systemic circulation through the damaged BBB, as well as increased intrathecal production. Furthermore, Q α2MG might be useful for the evaluation of BBB integrity.

A case of lymphomatosis cerebri mimicking inflammatory diseases.

BACKGROUND: Lymphomatosis cerebri (LC) is a rare subtype of primary central nervous system malignant lymphoma. The typical features of this disease exhibited on magnetic resonance imaging (MRI) without contrast enhancement are similar to those observed with diffuse leukoencephalopathy, mimicking white matter disorders such as encephalitis. Clinical features and examination findings that are suggestive of inflammatory diseases may indeed confound the diagnosis of LC. CASE PRESENTATION: A 66-year-old woman with continuous fever over a two-month period developed left hemiparesis despite presenting in an alert state with normal cognitive function. Sampling tests showed autoantibodies in the serum and inflammatory changes in the cerebrospinal fluid. The results from an MRI demonstrated multiple non-enhanced brain lesions in the splenium of the corpus callosum and deep white matter. Single photon emission computed tomography revealed increases in blood flow in the basal ganglia, thalamus and brainstem. No systemic malignancies were found. The patient was suspected of having a diagnosis of nonvasculitic autoimmune inflammatory meningoencephalitis and treated with intravenous methylprednisolone pulse therapy. Her fever transiently dropped to within the normal range. However, she had a sudden seizure and a second MRI exhibited infiltrative lesions gradually extending throughout the whole brain. We performed a brain biopsy, and LC was histologically diagnosed. The patient received whole-brain radiation therapy, which diminished the fever and seizures. The patient died one year after the initial onset of fever. CONCLUSIONS: The present case yields an important consideration that brain neoplasms, especially LC, cannot be ruled out, even in cases with clinical characteristics and examinations consistent with inflammatory diseases. Careful follow-up and histological study are vital for the correct diagnosis of LC.

Subgroup differences in 'brain-type' transferrin and α-synuclein in Parkinson's disease and multiple system atrophy.

Two transferrin (Tf) glycan-isoforms were previously found in cerebrospinal fluid (CSF); one appears to be derived from serum (Tf-2) and the other from choroid plexus, a CSF-producing tissue (Tf-1). To analyse metabolic differences associated with the two isoforms, their ratio (Tf-2/Tf-1) was defined as the Tf index. Here we report that Tf indices of patients with tauopathies including Alzheimer's disease (2.29 + 0.64) were similar to those of neurological controls (2.07 + 0.87) (P = 0.147). In contrast, Tf indices with Parkinson's disease (PD, 3.38 ± 1.87) and multiple system atrophy (MSA, 3.15 ± 1.72) were higher than those of the controls (2.07 ± 0.87), the P-values being < 0.001 and 0.024, respectively. Tf indices of PD and MSA did not appear to be normally distributed. Indeed, detrended normal Quantile-Quantile plot analysis revealed the presence of an independent subgroup showing higher Tf indices in PD and MSA. The subgroup of PD showed higher levels of CSF α-synuclein (38.3 ± 17.8 ng/ml) than the rest (25.3 ± 11.3 ng/ml, P = 0.012). These results suggest that PD (and MSA) includes two subgroups, which show different metabolism of CSF transferrin and α-synuclein.

Effects of L-Dopa and pramipexole on plasticity induced by QPS in human motor cortex.

Abnormal plasticity has been reported in the brain of patients with Parkinson's disease (PD), especially in the striatum. Although both L-Dopa and dopamine agonist remain to be the mainstay of the treatment in PD, their differential effects on cortical plasticity are unclear. We applied quadripulse stimulation (QPS) over the primary motor cortex (M1) in ten normal subjects to induce bidirectional long-term motor cortical plasticity. A long-term potentiation (LTP)-like effect was induced in the primary motor cortex (M1) by high-frequency QPS5 (interpulse interval of 5 ms) over M1, whereas a long-term depression (LTD)-like effect was induced by low-frequency QPS50 (interpulse interval of 50 ms), and the effects lasted up to 90 min after the stimulation pulses have ceased. In a double-blind randomized placebo-controlled crossover design, L-Dopa carbidopa 100 mg, pramipexole 1.5 mg [150 mg LED (L-Dopa equivalent dose)], or placebo was administered to the subjects 30 min before applying QPS. L-Dopa enhanced both LTP- and LTD-like plasticity as compared to placebo. In contrast, neither an LTP-like effect nor an LTD-like effect was modulated by pramipexole. The lack of LTP enhancement by pramipexole is compatible with the finding that D1 activation strengthens LTP because pramipexole is almost purely a D2 agonist. The lack of LTD enhancement by pramipexole is also consistent with the finding that both D1 and D2 coactivation is required for LTD. This is the first report to show that dopamine enhances LTD as well as LTP in the human brain and that coactivation of D1 and D2 is a requisite for LTD enhancement in normal humans.

[A patient with Fisher syndrome and pharyngeal-cervical-brachial variant of Guillain-Barré syndrome having a complication of SIADH].

A 69-year-old woman complained of diplopia and truncal titubation after upper respiratory infection. She presented with mydriasis and external opthalmoplegia of bilateral eyes, ataxia, hyporeflexia and cervical-brachial muscle weakness. The protein abnormally increased (49 mg/dl) in the cerebrospinal fluid, and the serum anti-GQ1b and anti-GT1a IgG antibodies were positive. The blood sodium level was 128 mmol/l indicating hyponatremia. She had low plasma osmolarity (251 mOsm/kg), high urine osmolarity (357 mOsm/kg) and high urine sodium level (129 mmol/l), while the blood level of antidiuretic hormone was not able to be measured. She was diagnosed to have Fisher syndrome (FS), pharyngeal-cervical-brachial variant of Guillain-Barré syndrome (PCB) and syndrome of inappropriate secretion of antidiuretic hormone (SIADH). The hyponatremia improved with hyperosmotic saline infusion and restriction of water intake. Intravenous immunoglobulin therapy (IVIg) was effective only for ataxia, but the other symptoms mostly remained unchanged for a month. The serum anti-GQ1b IgG antibody was still positive even after one month. We performed high-dose intravenous steroid-pulse therapy. Then the mydriasis, external opthalmoplegia and cervical-brachial muscle weakness were immediately improved. This was a rare case of FS and PCB complicated with SIADH. IVIg, not steroid therapy, is generally chosen for FS since FS is considered as a variant of Guillain-Barré syndrome and steroid is not effective for Guillain-Barré syndrome as was proven by double-blind study. We suppose that the combined therapy of IVIg and steroid would be effective in patients with complicated symptoms and multiple antibodies.

[Infliximab treatment trial in a patient with neuro-Behçet's disease unresponsive to other treatments].

A 22-year-old man with a previous uveitis episode was admitted to our hospital because of persistent hiccup. On admission, he presented right-upper quadrantanopia, mydriasis and lack of the light reflex in the left eye, left-sided hemiplegia, and bilateral pathologic hyperreflexia. The MR fluid attenuated inversion recovery images showed left side dominant, high intensity lesions on the brainstem and the diencephalon. The HLA-B51 was positive. The CSF IL-6 was extremely elevated (998 pg/ml: reference value < = 6.0 pg/ml). Based on these, we concluded he had the neuro-Behçet's disease and treated him by high dose intravenous corticosteroids. This treatment improved his symptoms and MRI lesions, and decreased the CSF IL-6 levels initially. On 13th day after the first his discharge, however, dysarthria appeared and the CSF IL-6 levels elevated again. In addition to the high dose intravenous corticosteroids therapy for acute attack, 15 mg/week of methotrexate was started to prevent the recurrence. Even with this prevention, meningitis related to neuro-Behçet's disease occurred within six weeks. We administered 5 mg/kg of infliximab intravenously at 0, 2, 6, and 14 weeks. After the infliximab treatment, his symptoms improved and the IL-6 levels decreased, and no recurrence has occurred. This case supports that infliximab, anti-TNF-alpha agent, is a good candidate for neuro-Behçet's disease treatment when it is resistant to conventional immunosuppressive agents such as corticosteroids or methotrexate.