Akioh Yoshihara

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.

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 Alzheimers disease (2.29 + 0.64) were similar to those of neurological controls (2.07 + 0.87) (P = 0.147). In contrast, Tf indices with Parkinsons 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.

Hemichorea-Hemiballism in a Patient with Temporal-Parietal Lobe Infarction Appearing After Reperfusion by Recombinant Tissue Plasminogen Activator

Hemichorea-hemiballism (HC-HB) is classically associated with stroke lesions in the STN. A large clinical study reported that some other lesions in the basal ganglia, such as in the caudate and putamen, may also cause HC-HB, which is seldom the result of a cortical infarction. We observed transient HC-HB in a patient with a cerebral infarction in the temporal-parietal lobe without any lesions in the basal ganglia including the STN after intravenous recombinant tissue plasminogen activator (rtPA) administration. A 72-year-old right-handed female, who had neither a history of diabetes mellitus nor dopaminergic medication use, was admitted to our hospital because of sudden-onset leftsided hemiparesis. Neurological examination revealed spatial disorientation, conjugate eye deviation to the right, and dysarthria. She had left-sided hemiparesis and sensory disturbance of all modalities. Deep tendon reflexes were exaggerated in the affected limbs. The plantar response was bilaterally flexor. National Institutes of Health Stroke Scale (NIHSS) was 19 points on admission. Blood sample tests were normal except for elevations of brain natriuretic peptide (717 pg/mL) and D-dimer (10.3 lg/mL). Thyroid function was normal, and hyperglycemia was ruled out. Brain MRIs showed acute cerebral infarction in the right temporal-parietal lobe perfused by the middle cerebral artery (MCA; Fig. 1A,B). Electrocardiogram showed atrial fibrillation. The patient was diagnosed as having cardioembolic infarction, and rtPA was administered within 3 hours after onset of symptoms. Nine hours later, her hemiparesis was improved significantly, which was reflected in the NIHSS score of 8 points (11-point decrease). Subsequent to motor improvement, the left hand started to show choreic movements, such as stereotypic pronation and supination, which progressed into ballistic arm movements in a day’s time. Eventually, the left-lower extremity was also involved, confirming HC-HB syndrome (Video 1). Subsequent brain MRIs confirmed no lesions in the basal ganglia, including the STN, and no changes in size of the stroke lesion (Fig. 1C,D). Single-photon emission CT (SPECT) showed an increase of blood flow in the right basal ganglia and hypoperfusion in the affected cortical lesion (Fig. 1E). These involuntary movements persisted and disappeared on the ninth day. She no longer exhibited neurological deficits thereafter. Five months later, follow-up brain MRIs revealed cortical laminar necrosis with atrophic changes in the stroke lesion, but no lesions in the basal ganglia (Fig. 1F). Hyperkinetic involuntary movements accompanied by a pure cortical infarction sparing the basal ganglia are extremely rare. The aforementioned large clinical study reported that only 6 cases of 5,007 consecutive stroke patients had hemichorea (0.12%), and the lesions were located in the MCA territory. In patients with an STN lesion, hyperkinetic disorder can be explained by dysfunction of the basal ganglia in the motor loop: Reduction of the striatopallidal inhibitory network by STN lesions leads to disinhibition of the thalamus and cortex, resulting in hyperkinetic involuntary movements. The mechanism of the cortical HC-HB has yet to be elucidated. A possible hypothesis proposes that interruption of the motor loop projection from the cortex to the basal ganglia by cortical infarctions might induce disparity of the excitatory and inhibitory neural network in the basal ganglia. Mizushima et al. reported HC-HB after a parietal lobe infarction. The brain MRI of this patient showed no basal ganglia lesions, but SPECT revealed hypoperfusion in the basal ganglia, indicating that ischemia of the basal ganglia may lead to functional imbalance and trigger HC-HB. A recent case series study showed 3 HC-HB cases that were associated with cerebral infarctions and reduction of blood perfusion in the frontal and parietal cortices sparing the basal ganglia. The researchers suggested a model of HC-HB induced by cortical lesions in which derangement of the corticocortical

Contrast medium injection into the spinal cord

Contrast medium injection into the spinal cord Akioh Yoshihara, Sachiko Namatame, Nozomu Matsuda and Yoshikazu Ugawa Department of Neurology, School of Medicine, Fukushima Medical University, Fukushima City, Fukushima, Japan, Department of Neurology, Ohara General Hospital, Fukushima City, Fukushima, Japan, and Fukushima Global Medical Science Center, Advanced Clinical Research Center, Fukushima Medical University, Fukushima City, Fukushima, Japan

Postictal Periorbital Petechial Rash

A 16-year-old boy, with a history of juvenile myoclonic epilepsy, which had been treated with valproic acid since he was 9 years of age, presented with bilateral periorbital rash. His family had found him in a stupor state after groaning early the previous morning. The patient had a history of morning myoclonic seizures and absence seizures, but no history of generalized tonic-clonic seizures. An electroencephalogram showed generalized polyspike-wave abnormalities. The results of neurological and physical examinations, including blood pressure, were normal and the routine laboratory data were unremarkable. The petechial rash on the bilateral periorbital regions (Picture) disappeared spontaneously within one week. Epilepsy-induced thoraco-cervicofacial purpura is a rare finding after generalized tonic-clonic seizures. It has previously been suggested that this finding may be caused by increased blood pressure or a high degree of congestion during the tonic-clonic phase, such as occurs in the Valsalva maneuver (1). This purpura may be a valuable indicator of epileptic seizure, even in the absence of other signs of epilepsy (2). Based on these arguments, we diagnosed this rash as a postictal periorbital petechial rash.

A case of lymphomatosis cerebri mimicking inflammatory diseases

BackgroundLymphomatosis 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 presentationA 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.ConclusionsThe 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.

46. Induction of human motor cortical long term plasticity by Octo-Pulse Stimulation (OPS)

ease (PD). Overall 9 MSA patients and 23 PD patients were investigated regarding presences of RBD symptom, REM sleep without atonia (RWA), and the proportion of RWA during PSG (%RWA) at two separate occasions. In MSA patients, %RWA significantly increased from the baseline to the follow up (16.0 ± 19.4% to 31.0 ± 27.7%) whereas numbers of patients with RWA and RBD symptoms unchanged. On the other hand, in PD patients, %RWA and numbers of patients with RWA and RBD symptoms did not change. In conclusion, RBD symptoms in MSA may decrease in association with the aggravation of MSA despite increase in %RWA. However, RBD symptoms in PD patients may not change with the clinical course of PD.