Antiphospholipid antibodies and cerebellar ataxia: a clinical analysis and literature review.

BACKGROUND: Although it has been established that antiphospholipid antibodies (APAbs) bind to and modulate the signaling of cerebellar neurons in vitro, the clinical correlation between increased APAbs and cerebellar ataxia has rarely been investigated. METHODS: We reviewed 10 patients presenting with cerebellar ataxia with increased blood APAbs from our database along with 3 APAb-associated cerebellar ataxia patients in the literature. RESULTS: Of these 10 patients, 4 exhibited a subacute onset of progressive ataxia, and there were no significant structural changes in their brains that appeared to be responsible for the symptoms. Another 6 showed a chronic course of ataxia, and shared similar morphological changes that included symmetrical lesions in bilateral hemispheres, periventricular lucency and central and temporal atrophy of varying severity; the cerebellum was spared. The predominant APAbs for subacute and chronic ataxia were the anti-beta2-glycoprotein I antibody and anticardiolipin antibody, respectively. Cancer was found in 1 patient with subacute ataxia and in 4 with chronic ataxia. The removal of the cancer, the plasmapheresis and immunosuppressive therapy successfully abolished the ataxia and increased APAb levels in all 5 patients. CONCLUSIONS: The relation between APAbs and nonvascular neurological disorders, such as cerebellar ataxia, should be further studied. APAbs may mediate neurological deficits via different mechanisms such as structural damage or functional neurotoxicity. Clinically, the examination of blood APAb levels is recommended for patients with cerebellar ataxia without a determined cause, and the further survey of systemic cancers in the case of APAb positivity is also recommended. Finally, plasmapheresis is a reasonable and effective treatment for APAb-associated cerebellar ataxia.

High performance liquid chromatography-tandem mass spectrometry method for ex vivo metabolic studies of a rhenium-labeled radiopharmaceutical for liver cancer.

The radio-isotope rhenium-labeled N-[2-(triphenylmethyl)thioethyl]-3-aza-19-ethyloxycarbonyl-3-[2-(triphenylmethyl)thioethyl] octadecanoate) ligand (188Re-MN-16ET) is a novel therapeutic agent under preclinical evaluation for hepatoma. A reversed-phase high performance liquid chromatography coupled with a tandem mass spectrometric analysis method and diode array detector (DAD) involving a T type splitter was developed to characterize this pharmaceutical in rat liver tissue solution and determine its biotransformation rate. The separation was accomplished on a C18 column (chromolith silica, 4.6 mm x 100 mm) using an acetonitrile-ammonium acetate buffer gradient as the mobile phase. The detection was achieved by DAD set at 250nm and tandem mass spectrometry using electrospray ionization in the positive ion mode. Re-MN-16ET displayed a retention time of 23.2 min and a transition ion pair corresponding to m/z677 --> 631 for multiple reaction monitoring. Its biotransformation reaction in rat liver homogenate proceeded for 90 min in a 37°C water bath. The characterization was conducted using aliquots that were extracted and concentrated from the reaction mixture for various incubation times. Re-MN-16ET exhibited a biotransformation half-life (t1/2) of 8-9 min in liver tissue solution and was almost completely exhausted after 90 min. Two of its metabolites, consisting of the Re-labeled carboxylic acid derivative, predominately, and its corresponding demetallized disulfide ligand were found in the liver homogenate, providing a metabolism pathway for the radio-pharmaceutical.

Periodic drop thumb, hypokalemia and adrenal adenoma.

OBJECTIVE: To report an unusual involvement of focal distal muscles but not proximal muscles in a patient with hypokalemic periodic paralysis (hypoPP). CLINICAL PRESENTATION AND INTERVENTION: A middle-aged woman presented with episodic weakness of the bilateral thumbs lasting for 2 years. Hypokalemia and a left adrenal mass were subsequently found. Her weakness subsided after surgical removal of the adrenal mass, which was pathologically proven to be an adrenal adenoma. CONCLUSION: The findings for this patient should alert physicians to consider focal distal motor paresis due to hypoPP. A preexisting occult trauma may predispose to paralysis at an atypical location in secondary hypoPP.

Association between MIF gene polymorphisms and carotid artery atherosclerosis.

Atherosclerosis is a chronic inflammatory disorder. Macrophage migration inhibitory factor (MIF) is a potent cytokine that plays an important role in the regulation of immune responses. Polymorphisms including five- to eight-repeat CATT variants ((CATT)(5-8)) and G-173C in the promoter region of the MIF gene are associated with altered levels of MIF gene transcription. The purpose of the study is to investigate the relationship between promoter polymorphisms of the MIF gene and the severity of carotid artery atherosclerosis (CAA). The severity of CAA was assessed in 593 individuals with a history of ischemic stroke by using sonographic examination, and the MIF promoter polymorphisms of these individuals were genotyped. The carriage of (CATT)7 (compared to genotypes composed of (CATT)5, (CATT)6, or both), carriage of C allele (compared to GG), and carriage of the haplotype (CATT)7-C (compared to genotypes composed of (CATT)5-G, (CATT)6-G, or both) were significantly associated with an increase in the severity of CAA. We conclude that polymorphisms in the MIF gene promoter are associated with CAA severity in ischemic stroke patients. These genetic variants may serve as markers for individual susceptibility to CAA.

Zoster sine herpete, vertebral artery stenosis, and ischemic stroke.

Although a previous or recent history of varicella-zoster virus (VZV) infection is known to increase the risk of stroke in both children and adults, the influence of zoster sine herpetic remains unclear. We report an immunocompetent man with common cold symptoms and conjunctivitis, followed by an acute onset of bulbar weakness and hemihypesthesia without preceding skin rash. Acute medullary infarction and left vertebral artery stenosis were detected. VZV infection was finally identified. Zoster sine herpetic interferes with accurate diagnosis of infectious stroke, and vertebral artery involvement is unusual in ischemic stroke in this situation. An unexplained course of ischemic stroke event should be suspected in patients with VZV cerebrovasculopathy, especially in those without conventional stroke risk factors and those exhibiting concomitant infectious complications.

Identification of the Hepatic Metabolites of Flumazenil and their Kinetic Application in Neuroimaging.

Studies of the neurobiological causes of anxiety disorders have suggested that the γ-aminobutyric acid (GABA) system increases synaptic concentrations and enhances the affinity of GABAA (type A) receptors for benzodiazepine ligands. Flumazenil antagonizes the benzodiazepine-binding site of the GABA/benzodiazepine receptor (BZR) complex in the central nervous system (CNS). The investigation of flumazenil metabolites using liquid chromatography (LC)-tandem mass spectrometry will provide a complete understanding of the in vivo metabolism of flumazenil and accelerate radiopharmaceutical inspection and registration. The main goal of this study was to investigate the use of reversed-phase high performance liquid chromatography (PR-HPLC), coupled with electrospray ionization triple-quadrupole tandem mass spectrometry (ESI-QqQ MS), to identify flumazenil and its metabolites in the hepatic matrix. Carrier-free nucleophilic fluorination with an automatic synthesizer for [18F]flumazenil, combined with nano-positron emission tomography (NanoPET)/computed tomography (CT) imaging, was used to predict the biodistribution in normal rats. The study showed that 50% of the flumazenil was biotransformed by the rat liver homogenate in 60 min, whereas one metabolite (M1) was a methyl transesterification product of flumazenil. In the rat liver microsomal system, two metabolites were identified (M2 and M3), as their carboxylic acid and hydroxylated ethyl ester forms between 10 and 120 min, respectively. A total of 10-30 min post-injection of [18F]flumazenil showed an immediate decreased in the distribution ratio observed in the plasma. Nevertheless, a higher ratio of the complete [18F]flumazenil compound could be used for subsequent animal studies. [18F] According to in vivo nanoPET/CT imaging and ex vivo biodistribution assays, flumazenil also showed significant effects on GABAA receptor availability in the amygdala, prefrontal cortex, cortex, and hippocampus in the rat brain, indicating the formation of metabolites. We reported the completion of the biotransformation of flumazenil by the hepatic system, as well as [18F]flumazenil's potential as an ideal ligand and PET agent for the determination of the GABAA/BZR complex for multiplex neurological syndromes at the clinical stage.

Peroxidase mimicking DNA-gold nanoparticles for fluorescence detection of the lead ions in blood.

Oligonucleotide (T30695) modified gold nanoparticles (T30695-Au NPs) have been prepared and employed for quantification of lead ions (Pb(2+)) in blood. The detection of Pb(2+) ions is through the formation of Au-Pb alloys and oligonucleotide-Pb(2+) complexes that catalyze the H(2)O(2)-mediated oxidation of non-fluorescent Amplex UltraRed (AUR) to form a highly fluorescent oxidized AUR product. Surface-assisted laser desorption/ionization time-of-flight mass spectrometry (SALDI-TOF MS) and inductively coupled plasma mass spectrometry (ICP-MS) revealed the formation of Au-Pb alloys on the surfaces of the 40T30695-Au NPs (i.e., the system featuring 40 molecules of T30695 per Au NP) in the presence of Pb(2+) ions, leading to increased catalytic activity for the H(2)O(2)-mediated oxidation of AUR. The fluorescence intensity (excitation/emission maxima: ca. 540/584 nm) of the oxidized AUR product is proportional to the concentration of Pb(2+) ions over the range 0.1-100 nM, with a linear correlation (R(2) = 0.99). The 40T30695-Au NP/AUR probe is highly selective toward Pb(2+) ions (by at least 200-fold over other tested metal ions). The 40T30695-Au NPs/AUR probe provided limits of detection (LOD, at a signal-to-noise ratio 3) for Pb(2+) ions of 0.05 and 0.1 nM, in Tris-acetate solution (5 mM, pH 8.0) without and with salt (150 mM NaCl, 5 mM KCl, 1 mM MgCl(2), and 1 mM CaCl(2)), respectively. Without conducting tedious sample pretreatment, the approach allows detection of Pb(2+) ions in blood samples, showing the potential of the 40T30695-Au NPs/AUR assay for on-site and real-time detection of Pb(2+) ions in biological samples.

The antemortem neurobehavior in fatal paramethoxymethamphetamine usage.

Paramethoxymethamphetamine (PMMA) is an emerging and prevalent psychoactive drug with a structure analogous to amphetamine and related psychostimulants. However, the neurobehavioral effect is only studied in experimental animals and is barely mentioned in human. The authors report the antemortem neurobehavioral manifestations in 8 patients with PMMA use. There were 2 different antemortem presentations. The first group of patients showed delirium, hypertalkativity, and incoherence speech and then turned into convulsion and death. They did not exhibit the typical hyperdopaminergic movement disorder. The second group of patients gradually fell asleep and then suffered respiratory or cardiovascular collapse. The heart blood PMMA level was higher in the second group than in the first group of patients. Forensic autopsy showed variable findings, ranging from no remarkable change to significant pathological damage similar to serotonin syndrome in both groups of patients. PMMA seems to enhance serotoninergism than dopaminergism, and exerts a concentration-related dual effect on human.

Successful amelioration of tinnitus in a stroke patient by low-dose gabapentin.

Bilaterally progressive tinnitus and hearing impairment occurred in a hypertensive patient shortly after an episode of right ganglionic hemorrhage. Audiometric tests showed a mixed sensorineural and conduction hearing loss. When low-dose gabapentin was administrated for the pre-existing postherpetic thoracic neuralgia, the tinnitus dramatically improved but recurred after discontinuation of the drug. Hearing function did not change. In view of a controversy of gabapentin and tinnitus in previous trials, the findings in this patient support that low-dose gabapentin benefits the subgroup of tinnitus patients with secondary contributing factors, such as stroke.

Ischemic stroke after low-voltage electric injury in a diabetic and coagulopathic woman.

Electric injury is a common physical injury in daily life. Because of the low resistance of vascular tissue, vascular injury and thrombosis are frequently found in cases of high-voltage electric injury but are rarely reported in low-voltage conditions. We present the case of a diabetic woman who suffered symptomatic brainstem stroke after a short duration of 60 Hz/110 V alternate current electric contact with a home washer socket. A stroke risk factor survey did not reveal remarkable cardiac or vascular abnormality, except increased glycohemoglobin levels and decreased protein C activity. In contrast to a direct and adequate energy transfer in high-voltage electric injury, a pre-existing vasculohemostatic deficit, such as coagulopathy, has been proposed to provide a predisposition to thrombosis in low-voltage electric injury. Nevertheless, the findings in this patient remind the possibility of physical triggering factor for stroke occurrence in our environment as new technology and product generates rapidly enough for understanding their safety and biologic effect.

Symptomatic noncompressive motoromyelopathy presents as early manifestation in ankylosing spondylitis.

Ankylosing spondylitis (AS) is an autoimmune spondyloarthropathy involving principally the sacroiliac joint and axial skeleton. Spinal cord involvement is an infrequent and late complication. It mostly results from compressive myelopathy due to skeletal osteopathy and usually presents with radiculomyelopathic sensory and motor deficits. To report three patients who suffered a progressive paraparesis/tetraparesis compatible with motor myelopathy without typical skeletal symptom. Myelopathy of unknown origin was initially interpreted in these patients. Radiography did not show typical change at sacroiliac joint or vertebrate. Spinal magnetic resonance image revealed cord atrophy at cervical and thoracic segment. A positivity of B27 antigen was found afterward. Their spondyloarthropathic symptoms developed within six months later with radiographic sacroiliitis. Seropositive AS with noncompressive myelopathy was finally established. Patients showed a reverse of motor impairment when their pain was well undercontrolled. Motor myelopathy may be neglected or underestimated in AS, in especially when typical skeletal symptom is absent or minimal. It may progress surreptitiously to harm spinal function or superimpose to crippling disability in compressive spinal cord injury. Therefore, a careful evaluation and monitor of spinal cord function is important for AS patient despite spinal deformity is not observed.

The medicolegal issue of tissue plasminogen activator in ischemic stroke: a review of judiciary decrees in Taiwan.

PURPOSE: Tissue plasminogen activator (tPA) was approved by the Food and Drug Administration for ischemic stroke treatment since 1996 at the United States of America and also 2002 at Taiwan. Since after it is strongly advertised for a promising benefit to early thrombolysis that is further echoed by a recommendation in clinical guidelines from multiple medical associations in worldwide. Because of an overwhelming data of positive benefit collected in the evidence-based medicine database, legal dispute subsequently occurs when tPA is failed to be administrated in appropriate time. METHODS: In order to elucidate the legal viewpoint for tPA used in ischemic stroke, a review of the domestic judiciary decrees regarding this issue was conducted. Cases in Taiwan were executed from the open access database of the Judicial Yuan, Taiwan. The background, legal dispute and judgment of each case were analyzed. RESULTS: Till August, 2010, there were 6 cases in Taiwan. All cases occurred after 2003. The causes of disputes were a loss of chance for thrombolysis due to a delay of diagnosis (4 cases, 67%) and a failure of thrombolytic treatment after a diagnosis of ischemic stroke (2 cases, 23%). All cases were presented to non-neurologists at initial. Five cases expired or terminated into vegetation before litigation. CONCLUSION: A failure of early diagnosis or treatment after a diagnosis of ischemic stroke are important for medicolegal dispute in tPA usage, which is expected to become prevalent in Taiwan in future. A fatal or poor outcome may be a triggering factor for litigation. Therefore, an improvement of the knowledge and practice to increase early diagnosis of ischemic stroke is the key factor for reducing medicolegal issue regarding tPA use in ischemic stroke. This is particularly true for non-neurologist physicians.

Spinal cheiro-oral syndrome: a common neurological entity in an unusual site.

BACKGROUND AND PURPOSE: Cheiro-oral syndrome (COS) is an established neurological entity characterized by a sensory impairment confined to the mouth angle and ipsilateral finger(s)/ hand. The current understanding of localization is a concomitant involvement of the spinothalamic and trigeminothalamic tract between the cortex and pons. The cervical spinal cord has not been mentioned in this situation yet, and this unusual location may heretofore increase the risk of misdiagnosis. MATERIAL AND METHODS: Six patients who presented with unilateral COS due to cervical cord disorder are reported. RESULTS: All patients were women and their age ranged between 42 and 70 years. Their neurological deficits included unilateral paraesthesiae restricted to cheirooral distribution, positive radicular sign, and mild change of tendon reflex. Cervical spinal stenosis at middle/lower cervical spine with variable magnitude of cord compression and intrinsic cord damage was found. A diagnostic dilemma obviously arises from the lack of tangible neurological signs or typical pattern of myelopathy, in addition to the previous concept of cerebral involvement. A benign course ensued in all reported patients. CONCLUSIONS: Cheiro-oral syndrome can be an early neurological sign for cervical cord disorder; it further suggests that it is a strong neurological but weak localizing sign. A reciprocal influence of multiple factors is considered to generate COS at the cervical cord. Therefore, an absence of brain pathology should lead to a thorough examination of the cervical cord in case of COS.

Comparison of carotid artery stenting performance between cardiologists and neuroradiologists: one medical center's experience.

PURPOSE: To report the experience of carotid artery angioplasty with stenting (CAS) by cardiologists (CV) and neuroradiologists (NR) in an area with less incidence of extracranial artery stenosis. METHODS: From 1999 to 2008, 210 patients with 231 stents were collected by claim records from the administrative office and reviewed by one independent neurologist. Outcome measures were peri-procedural adverse events (AE), restenosis and recurrent ipsilateral stroke (RS) rate, categorized into treatment groups by either CV or NR. RESULTS: The average age was 69.0 years and 82.9 % of the patients were men. 63.8% of the patients with 62.8% stents were treated by CV and the remaining 36.2% of patients with 37.2% stents were done by NR. Symptomatic CAS was evident in 70.1% of the CV cases and 83.0% in NR treated patients (P = 0.017). The peri-procedural AE rate was 31.6%; 35.9% in CV group and 24.4% in the NR group (P = 0.071). RS rate was 4.8% in 663.3 days; 4.1% in 920.8 days in the CV group and 5.8% in 354.2 days in the NR group (P = 0.865). The restenosis rate was 10.9% in 630.5 days; 5.4% in the CV group in 224.8 days and 20.6% in the NR group in 817.8 days (P = 0.007). CONCLUSIONS: The restenosis and recurrent stroke rates after carotid artery stenting in Taiwan appears to be consistent with other published and well organized trials. Measures to minimize peri-procedural AR rates are definitely warranted.

Antiphospholipid antibody, head-shaking and ataxia: an evidence of non-vascular neurotoxicity and successful treatment by plasmapheresis.

Although antiphospholipid antibodies (APAbs) are considered to possess neurotoxic property, their relation with non-vascular neurological disorder is still disputed. This dilemma is mainly due to only a cross-sectional analysis or sporadic pictorial description in previous reports. In addition, treatment strategy is unknown in this situation. We encountered a patient who exhibited head-shaking and cerebellar ataxia had an increase of blood anti-beta2-glycoprotein I antibody and anticardiolipin antibody. Her neurological deficits did not respond to corticosteroid pulse therapy but rapidly subsided after plasmapheresis associated with a normalization of APAbs. Accordingly, a causal relation between APAbs and non-vascular neurological disorder is favored. The pathogenesis of APAb-related non-vascular neurotoxicity is warranted for further study to avoid premature conclusion. Plasmapheresis is recommended when movement disorder responds poorly to conventional treatment, especially when APAb is found.

Cheirobuccopedal syndrome.

OBJECTIVES: Restricted sensory syndrome provides an excellent chance for the understanding of neuroanatomic correlation. The trigeminal nerve has been shown to convey buccal sensory impulse to central compartment. However, the pathway between cortex and the trigeminal sensory nucleus remains largely unknown. METHOD: A patient presented with cheirobuccopedal syndrome, or objective sensory impairment confined to the left intraoral cheek, hand and foot, was reported. RESULTS: Decrease in pinprick pain and fine touch sensation was detected at the left intraoral cheek, hand and foot. A recent infarction was disclosed at the left paramedian pons. The foregoing hypalgesia and hypesthesia recovered within one month after onset. DISCUSSION: The trigeminobuccal sensory tracts are deemed to run in parallel with other spinothalamic and trigeminothalamic tracts within the brainstem. The rarity of buccal sensory deficit upon brainstem damage may be due to dispersion of the trigeminobuccal sensory tracts on their way of ascending, or their relatively high tolerance to different insults.

Clocking tinnitus: An audiology symptom of migraine.

OBJECTIVES: In contrast to previous concept that tinnitus is confined to an otologic disorder, current evidence supports it as a phantom sensory phenomenon of vestibulocochlear damage with cortical reorganization. It is a common problem worldwide, but the treatment response is always unsatisfactory. PATIENTS AND METHODS: In this study, we report 10 patients who described their staccato tinnitus as simulating the ticking sound of a pendulum or quartz clock (or termed clocking tinnitus). The tinnitus characteristics, laboratory tests, and treatment response were recorded. RESULTS: Clocking tinnitus was unilateral in three patients, bilateral in one patient, and at midline in another six patients. It usually subsided within 15 min. Neither patient experienced vertigo, hemifacial spasm, focal neurological deficit or otic disorder in association with tinnitus. Pre-existing migraine was present in seven patients. During tinnitus attack, a few migraine symptoms concurrently occurred in six patients. Pure-tone audiometry showed symmetric sloping pattern of hearing impairment in half patients whereas brainstem auditory evoked potentials revealed a prolonged wave I-III latency in 30% of patients. The p300 and electroencephalogram were normal in all of them. Neuroimaging study did not disclose structural change. All patients responded poorly to conventional treatments but favorably to flunarizine or topiramate. CONCLUSION: Clocking tinnitus may be an audiology manifestation of migraine in some individuals. Antimigraine treatment can be considered in this specific group of staccato tinnitus. Audiogenic classification of tinnitus may provide diagnostic and treatment clues in tinnitus patients.

Crossed cheiro-oral syndrome.

OBJECTIVES: Cheiro-oral syndrome is characterized by sensory impairment confined to perioral area and ipsilateral fingers/hand. It results from an involvement of the ascending sensory tracts above the pons. However, a crossed pattern of perioral and acral paresthesia was rarely reported before. PATIENTS AND METHODS: This study reports the neuroanatomic relationship, course and clinical significance of perioral and contralateral acral paresthesia in four patients. We term it the crossed cheiro-oral syndrome. RESULTS: All patients had lateral or dorsolateral medullary infarctions that were ipsilateral to their perioral paresthesia. The contributory origin is considered a diagonal lesion involving the par oralis fibers within the descending trigeminal sensory tract and acral portion of the lateral spinothalamic tract at the lateral portion of medulla oblongata. Despite of a restricted sensory disturbance at initial, progressive neurological disability terminated to Wallenberg's syndrome ensued in three patients and disabling deficits persisted in two of them. CONCLUSION: The crossed cheiro-oral syndrome seems a mild form of Wallenberg's syndrome. Therefore, it predicts medullary involvement and is also a warning sign for progression.

Type II cryoglobulinemia and brain hemorrhage.

By virtue of an understanding of hemostasis and coagulopathy using modern techniques, the exact role of individual serum protein in vascular thrombosis or hemorrhage becomes more apparent. Cryoglobulin causes vasculitude and thrombosis in various vascular beds, but its role in brain hemorrhage is unknown. We encountered a cryoglobulinemic patient to have cryoglobulinemia, hypocomplementia, and cerebellar hemorrhage during a reactivation of cytomegalovirus infection. Because cryoglobulin is harmful to vessel and hemostasis, and often increases nonspecifically in response to incitement, its weight in vascular syndrome must seriously be reviewed. Coagulopathy in a reactivation of latent virus such as cytomegalovirus should be cautioned in older patients.

Characterization of dilute acid pretreatment of silvergrass for ethanol production.

Pretreatment with dilute sulfuric acid of silvergrass was compared with the pretreatment's effect on other commonly used lignocellulosic materials, namely rice straw and bagasse, in order to evaluate the potential of this feedstock for ethanol production. The highest yield of xylose from silvergrass was between 70% and 75%, which was similar to bagasse. However, silvergrass gave a higher level of fermentability than bagasse using the hydrolysate because less acetic acid was formed. The release of sugars resulted in an about 2.0-fold increase in specific surface area of the pretreated silvergrass. Increasing the specific surface area did not obviously enhance enzymatic digestibility. The hydrophilicity of the acid pretreated silvergrass was characterized using its Fourier transform infrared (FTIR) spectra. The increase in hydrophilicity may enhance enzymatic adsorption onto lignin and increase the accumulation of cellobiose for enzymatic hydrolysis as pretreatment severity increases.