More than a piece of cake: Noun classifier processing in primary progressive aphasia.

INTRODUCTION: Clinical understanding of primary progressive aphasia (PPA) has been primarily derived from Indo-European languages. Generalizing certain linguistic findings across languages is unfitting due to contrasting linguistic structures. While PPA patients showed noun classes impairments, Chinese languages lack noun classes. Instead, Chinese languages are classifier language, and how PPA patients manipulate classifiers is unknown. METHODS: We included 74 native Chinese speakers (22 controls, 52 PPA). For classifier production task, participants were asked to produce the classifiers of high-frequency items. In a classifier recognition task, participants were asked to choose the correct classifier. RESULTS: Both semantic variant (sv) PPA and logopenic variant (lv) PPA scored significantly lower in classifier production task. In classifier recognition task, lvPPA patients outperformed svPPA patients. The classifier production scores were correlated to cortical volume over left temporal and visual association cortices. DISCUSSION: This study highlights noun classifiers as linguistic markers to discriminate PPA syndromes in Chinese speakers. HIGHLIGHTS: Noun classifier processing varies in the different primary progressive aphasia (PPA) variants. Specifically, semantic variant PPA (svPPA) and logopenic variant PPA (lvPPA) patients showed significantly lower ability in producing specific classifiers. Compared to lvPPA, svPPA patients were less able to choose the accurate classifiers when presented with choices. In svPPA, classifier production score was positively correlated with gray matter volume over bilateral temporal and left visual association cortices in svPPA. Conversely, classifier production performance was correlated with volumetric changes over left ventral temporal and bilateral frontal regions in lvPPA. Comparable performance of mass and count classifier were noted in Chinese PPA patients, suggesting a common cognitive process between mass and count classifiers in Chinese languages.

Acute Asymmetric Sensorimotor Variant of Chronic Inflammatory Demyelinating Polyneuropathy Triggered by mRNA-1273 COVID-19 Vaccination.

PURPOSE: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) developing in the postvaccination period was distinctly unusual and its course was rarely well described. We aimed to clearly depict the clinical features of acute-onset multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) caused by mRNA-1273 COVID-19 vaccination. CASE REPORT: A 74-year-old man noticed weakness of hands 2-3 days after he accepted the second dose of mRNA-1273 COVID-19 vaccine. He soon became unable to walk within one week. Initially, muscle power of bilateral hand grasping was most severely affected. He had stayed on at the nadir for 3.5 months until the diagnosis of CIDP was made. Nerve conduction studies showed typical evidences of acquired demyelinating, but no sural spare pattern. He was treated with intermittent pulse steroid therapy. Two weeks after treatment, INCAT disability score improved from 10 to 4, but remained at 4 thereafter: arm disability score was 3 and that of leg was 1, which suggested muscles of upper limbs were more severely affected. CONCLUSION: Diagnosis of acute-onset MADSAM was challenging at the beginning of this disease. For vaccine-triggered CIDP, time to symptom onset could be as short as 2-3 days. Delay in recognition may influence the remission of this disease. Muscles of upper limbs were more affected than those of lower limbs. Intermittent steroid pulse therapy would be an alternative to daily oral steroid therapy. Keyword: chronic inflammatory demyelinating polyradiculoneuropathy, COVID-19 vaccination.

The Clinical Course of New-Onset Ocular Myasthenia Gravis Caused by Pfizer-BioNTech COVID-19 Vaccine.

PURPOSE: Myasthenia gravis (MG) caused by COVID-19 vaccine had been reported, but the clinical course of new-onset ocular MG had never been described. We would like to document the clinical course of a patient with new-onset ocular MG which was caused by Pfizer-BioNTech COVID-19 vaccine. CASE REPORT: A 39-year-old woman noticed diplopia one week after she accepted the first dose of Pfizer- BioNTech COVID-19 vaccine. Diagnosis of ocular MG was made after investigation. Despite intravenous immunoglobulins, pyridostigmine and prednisolone therapy, she had no improvement until 10 days after treatment. She then rapidly improved, and almost fully recovered in the following 10 days. We had observed this patient for 8 months. After tapering off steroid, she remained stable to date, though she still suffered from transient diplopia on awakening. CONCLUSION: No matter the symptoms at onset, the clinical course or the response to steroid therapy was identical to ocular MG that we had ever known. Ocular MG caused by COVID-19 vaccine could probably be an iatrogenic life-long disease.

Prognostic Features of Sporadic Creutzfeldt-Jakob Disease: An Analysis of Taiwan's Nationwide Surveillance.

OBJECTIVES: To study the prognostic features of Creutzfeldt-Jakob disease (CJD) and shed light on its future therapy. DESIGN: Retrospective cohort study of a longitudinal national cohort of the Taiwan Centers for Disease Control. SETTING AND PARTICIPANTS: All patients with suspected CJD are reported to the CJD surveillance unit of the Taiwan Centers for Disease Control. An expert committee discussed the reported cases and designated a consensus-based diagnosis. From 1996 to 2020, a total of 809 cases were referred to the CJD surveillance unit for confirmation; of these, 441 cases (women, n = 230) were determined to be sporadic CJD. METHODS: We investigated the clinical manifestations and laboratory findings for 400 patients diagnosed with definite or probable sporadic CJD. We used Kaplan-Meier analyses and Cox proportional hazards model to identify prognostic factors. RESULTS: The mean age of onset was 67 ± 9.9 years. The mean survival duration was 13.3 ± 14.2 (median 10) months. The leading clinical symptoms were myoclonus (73%) and akinetic mutism (54%). For PRNP polymorphism, 99% of patients (195/197) showed a methionine homozygous genotype at codon 129 (M129M). The sensitivity of periodic sharp wave complexes (PSWCs) on electroencephalograms (EEGs) was 59.7%. The sensitivity of cerebrospinal fluid 14-3-3 protein and total tau protein (>1200 pg/mL) were 69.7% and 75.6%, respectively. Younger patients lived longer than those aged ≥65 years [hazard ratio (HR) 0.466, P < .001]. Women had a better survival probability in the first 3 years than their male counterparts (HR 0.712, P = .005). PSWCs had a persistent negative effect on survival (HR 0.788, P < .05). Although uncommon, epileptic seizures were the only clinical prognostic factor for survival time (HR 0.768, P < .05). PSWCs can be used as an EEG biomarker for prognosis. Epileptic seizures, though not common, are the only clinical prognostic factor for a short survival. CONCLUSIONS AND IMPLICATIONS: We found that a lower age of onset and female gender favor the survival of patients with sCJD. PSWCs are EEG biomarkers unfavorable for survival, and so are epileptic seizures.

Effectiveness of the WHO-Authorized COVID-19 Vaccines: A Rapid Review of Global Reports till 30 June 2021.

Large clinical trials have proven the efficacy of the COVID-19 vaccine, and the number of studies about the effectiveness rapidly grew in the first half of the year after mass vaccination was administrated globally. This rapid review aims to provide evidence syntheses as a means to complement the current evidence on the vaccine effectiveness (VE) against various outcomes in real-world settings. Databases (PubMed, EMBASE, and MedRxiv) were searched up to 30 June 2021, (PROSPERO ID: 266866). A total of 39 studies were included, covering over 15 million participants from 11 nations. Among the general population being fully vaccinated, the VE against symptomatic SARS-CoV-2 infection was estimated at 89-97%, 92% (95% CI, 78-97%), and 94% (95% CI, 86-97%) for BNT162b2, ChAdOx1, and mRNA-1273, respectively. As for the protective effects against B.1.617.2-related symptomatic infection, the VE was 88% (95% CI, 85.3-90.1%) by BNT162b2 and 67.0% (95% CI, 61.3-71.8%) by ChAdOx1 after full vaccination. This review revealed a consistently high effectiveness of certain vaccines among the general population in real-world settings. However, scarce data on the major variants of SARS-CoV-2 and the shortness of the study time may limit the conclusions to the mRNA vaccines and ChAdOx1.

Incidence of and Mortality Due to Human Prion Diseases in Taiwan: A Prospective 20-Year Nationwide Surveillance Study from 1998 to 2017.

INTRODUCTION: Epidemiologic studies of Creutzfeldt-Jakob disease (CJD) have been undertaken worldwide since the new variant CJD outbreak in 1996 in the United Kingdom. A nationwide report system, the Creutzfeldt-Jakob Disease Surveillance Unit (CJDSU), directed by the Centers for Disease Control of Taiwan, was established in 1997 to identify human prion diseases. METHODS: From 1998 to 2017, 647 cases were referred to the committee for confirmation. The report to CJDSU included a structured questionnaire recording the clinical, demographic data, and potential iatrogenic exposure, and the results of the clinical and laboratory examination, including tests of blood and cerebrospinal fluid, electroencephalography, and brain magnetic resonance imaging. RESULTS: In total, 356 cases (women, n=178) were ascertained to be human prion diseases, and 97.4% (n=347) were sporadic CJD, including three definite, 314 probable, and 30 possible cases; one probable variant CJD and 8 cases of the genetic form human prion diseases. The age- and gender-specific average annual incidence were also significantly higher in the second decade (0.95/1,000,000) than in the first decade (0.63/1,000,000), with an incidence rate ratio of 1.51. The incidences increased with increasing age, reaching a peak at the age of 70-79 years. The 10-year survival curve for sCJD patients showed that the 1-, 5-, and 10-year cumulative survival rate were 52%, 5%, and 1%, respectively. PRNP polymorphisms in 170 patients showed that 98.8% were M129M and 97.6% E219E. DISCUSSION: The significant increase in incidence after 2008 suggests the increase in the awareness of this rare disease among physicians. The longer disease duration in patients with sCJD in Taiwan than in other countries indicates that the comprehensive support of the health care system, as well as the end-of-life care culture in Taiwan, may prolong survival time in patients with such a progressive and fatal disease.

Long-term and Strong Immunotherapy to Treat Anti-N-Methyl- D-Aspartate Receptor Encephalitis with Refractory Status Epilepticus.

BACKGROUND: Anti-N-Methyl-D-Aspartate receptor (anti-NMDAR) encephalitis is responsive to immunotherapy and removal of tumor, but there is no consensus in the treatment of severe anti- NMDAR encephalitis with prolonged refractory status epilepticus (SE). CASE REPORT: A 17-year-old girl presented as acute psychosis, refractory seizures, hyperkinesia, autonomic instability, and soon progressed to a dissociative state of coma. Anti-NMDAR antibodies were positive in serum and CSF. When most of the symptoms were alleviated after repeated one-byone immunotherapy during the first four months, the patient still remained in a coma with frequent seizures despite treatment with five different anti-epileptic drugs. We then proposed a three-combined immunotherapy of high-dose steroid, intravenous immunoglobulin and rituximab. After such treatment, her SE was soon resolved and this patient regained her consciousness before resection of ovarian teratoma. Although she had suffered from a prolonged period of refractory SE and coma for six months, she still had good recovery from encephalitis after a long-term immunotherapy. CONCLUSION: A strong and long-term course of immunotherapy is necessary in treating severe refractory anti-NMDAR encephalitis. If traditional step-by-step way of immunotherapy is not strong enough to rapidly cure severe anti-NMDAR encephalitis, combined immunosuppressive agents can be considered to shorten the clinical course.

Association Between Zolpidem and Suicide: A Nationwide Population-Based Case-Control Study.

OBJECTIVE: To evaluate the association between zolpidem and the risk of suicide. PATIENTS AND METHODS: In this nationwide case-control study, the case group comprised 2199 people who committed suicide or were hospitalized due to suicide attempt between January 1, 2002, and December 31, 2011. To create a control group, we randomly selected 10 people matched to each case according to age, sex, urbanization, and occupation. We measured the risk of suicide/suicide attempt in association with zolpidem exposure by using adjusted odds ratios (ORs) and assessed the dose-response effect of zolpidem. RESULTS: After adjustment for potential confounders such as the comorbidities of schizophrenia, major depression, bipolar disorder, anxiety, insomnia, substance use, and other mental disorders, the Charlson comorbidity index, and use of benzodiazepine or antidepressants, zolpidem exposure was found to be significantly associated with the risk of suicide/suicide attempt with an OR of 2.08 (95% CIs, 1.83-2.36). The risk increased with the level of zolpidem use. The ORs (95% CIs) for cumulative defined daily doses of less than 90, 90 to 179, and 180 mg or more were 1.90 (1.65-2.18), 2.07 (1.59-2.67), and 2.81 (2.33-3.38), respectively (for trend, P<.001). Subgroup analyses showed that the exposure to zolpidem consistently increased the OR in different age groups, sex, urbanization level, occupation, mental disorders, and Charlson comorbidity index levels and in groups of people with or without the presence of insomnia. CONCLUSION: This study demonstrated a significant association between using zolpidem and suicide or suicide attempt in people with or without comorbid psychiatric illnesses (all P<.05).

Risk of Amyotrophic Lateral Sclerosis in Patients With Diabetes: A Nationwide Population-Based Cohort Study.

BACKGROUND: Glucose intolerance in patients with amyotrophic lateral sclerosis (ALS) has been inconsistently reported. Evidence for the association of ALS and diabetes mellitus is limited. We aimed to assess the overall and age- and sex-specific risks of ALS among patients with diabetes in Taiwan. METHODS: The study cohort included 615 492 diabetic patients and 614 835 age- and sex-matched subjects as a comparison cohort, followed from 2000 to 2008. We estimated the incidence densities of ALS and calculated the relative hazard ratios (HRs) of ALS (ICD-9-CM 335.20) in relation to diabetes using a Cox proportional hazard regression model, with adjustment for potential confounders, including sex, age, geographic area, urbanization status, Charlson Comorbidity Index, frequency of medical visit, and histories of hypertension, hyperlipidemia, and chronic obstructive pulmonary disease. RESULTS: Over a 9-year period, 255 diabetic and 201 non-diabetic subjects developed ALS, corresponding to incidence densities of 7.42 and 5.06 per 100 000 person-years, respectively. After adjustment for potential confounders, patients with diabetes experienced a significantly elevated HR of 1.35 (95% confidence interval [CI], 1.10-1.67). A higher covariate adjusted HR was noted in men (HR 1.48; 95% CI, 1.13-1.94) than in women (HR 1.17; 95% CI, 0.84-1.64), while men aged ≤65 years showed the most increased HR of 1.67 (95% CI, 1.18-2.36). CONCLUSIONS: This study demonstrated a moderate but significant association of diabetes with ALS onset, and such association is not confounded by socio-demographic characteristics or certain ALS-related co-morbidities. Further studies are warranted to examine whether the findings observed in our study can be replicated.

Risk of stroke with thiazolidinediones: a ten-year nationwide population-based cohort study.

BACKGROUND: Thiazolidinediones (TZDs) - rosiglitazone and pioglitazone - a class of insulin sensitizer for treating type 2 diabetes, have been reported to exhibit neuroprotective effects in preclinical studies and have good effects in the control of blood sugar for diabetic patients with insulin resistance. However, clinical trials and observational studies have raised the possibility of higher stroke risk in patients treated with rosiglitazone. Whether pioglitazone poses similar stroke risk remains uncertain. Most of the studies on cardiovascular effects of TZDs were based on studies in the USA and Europe. The present study aimed to compare the stroke risk among diabetic patients on TZD to those on non-TZD medications in an Asian population. METHODS: The study cohort included 15,981 patients with a diagnosis of diabetes without prior stroke, acute myocardial infarction (AMI) or heart failure who were followed from 2001 to 2010. Patients were classified by their prescriptions into rosiglitazone, pioglitazone and non-TZD groups. The study end points included ischemic and hemorrhagic stroke. In view of the reported association of heart failure and AMI with rosiglitazone, these 2 end points were also included in the present study. Cox hazard proportional models were used to estimate the risk of developing the end points. Likelihood ratio test was used to examine the age-drug interactions. Dose-response effects were evaluated by comparing the incidence rates among patients with different cumulative exposures to TZD. RESULTS: During the 10-year follow-up, the rosiglitazone group showed significantly higher risk of ischemic stroke (multivariate adjusted hazard ratio, HR = 1.39; 95% confidence interval, CI = 1.16-1.66) and heart failure (HR = 1.59; 95% CI = 1.18-2.14) than the non-TZD group. The pioglitazone group did not show significant difference from the non-TZD group in ischemic stroke (HR = 0.97; 95% CI = 0.75-1.26) and heart failure (HR = 0.94; 95% CI = 0.59-1.50). The results also showed a significant dose-dependent effect of higher risk of ischemic stroke with increasing dosage of rosiglitazone, while there was no increased risk at any level of pioglitazone dosage. CONCLUSIONS: This population-based cohort study shows that rosiglitazone imposes a higher risk of developing stroke or heart failure in this Asian patient population, suggesting the adverse side effects of rosiglitazone across ethnic boundaries. Pioglitazone, on the other hand, does not increase cardiovascular or stroke risk compared to the non-TZD group among diabetic patients without a history of macrovascular disease.

Prediction of infarct growth and neurologic deterioration in patients with positive perfusion-diffusion mismatch.

BACKGROUND: To assess the value of baseline clinical severity and perfusion-diffusion mismatch as predictors for further infarct growth and clinical outcome. METHODS: Patients with acute ischemic stroke and initial perfusion-diffusion mismatch within 72 h were enrolled. Baseline perfusion defects on time-to-peak (TTP) and cerebral blood volume (CBV) maps were measured. Infarct volume and stroke severity were assessed by diffusion-weighted image (DWI) and NIHSS, and were repeatedly assessed 7 days later. The predictive value of baseline NIHSS and perfusion defects on further infarct growth and neurologic deterioration was determined. RESULTS: Fifty-two patients (mean age 68.3±12.8 years, 42% women) were enrolled. CBV defects were significantly associated with infarct growth (CBV, p=0.02). Initial stroke severity, but not TTP and CBV mismatch (p=0.65 and 0.76, respectively), significantly inversely correlated with neurologic deterioration (p=0.001). CONCLUSIONS: In patients with mismatch, those with severe symptoms initially are more likely to have infarct growth, while those with minor symptoms tend to suffer from larger extent of neurologic deterioration within 1 week. CBV is associated with further infarct growth but not clinical deterioration.

Lack of association between total serum homocysteine and extracranial cerebral flow.

BACKGROUND/PURPOSE: High homocysteine (Hcy) concentration is associated with slow coronary flow. This study examined the association between Hcy and hemodynamic status in the extracranial cerebral arteries in healthy individuals. METHODS: A total of 535 healthy adults underwent physical examination and duplex ultrasonography of the extracranial carotid and vertebral arteries, and blood laboratory tests, including biochemistry and serum total Hcy. Flow hemodynamic parameters including velocity, resistance, and volume of the carotid and vertebral arteries were measured. Multiple regression analysis was performed to examine the association between Hcy and the flow parameters. RESULTS: Participants with higher Hcy were more likely to have a lower systolic velocity of the internal carotid artery (p = 0.01) and vertebral artery (p < 0.001), and lower resistance of the vertebral artery (p = 0.004). However, the multiple-adjusted means of the flow velocity, resistance, and flow volume of the carotid or vertebral artery were not significantly different across quartiles of Hcy. When Hcy was treated as a continuous variable, there was still no significant relationship between Hcy levels and the aforementioned hemodynamic status. CONCLUSION: Our results did not support the hypothesis that the levels of Hcy are associated with the flow velocity, resistance, and volume of the extracranial cerebral artery in healthy individuals.

Incidence of Creutzfeldt-Jakob disease in Taiwan: a prospective 10-year surveillance.

This study was performed to estimate the incidence of Creutzfeldt-Jakob Disease (CJD) in Taiwan from 1998 to 2007. Suspected cases of CJD were reported to the Taiwan Creutzfeldt-Jakob Disease Surveillance Unit, a nationwide, hospital-based case report system initiated since 1996 to prospectively conduct a CJD epidemiological study. Consecutive patients who met the diagnostic criteria recommended by the World Health Organization were enrolled. The clinical information of each suspected case was collected and case ascertainment was performed by an expert committee. A total of 123 sporadic CJD were identified without any iatrogenic or new variant CJD cases. The overall annual incidence rate (95% CI) was 0.55 (0.46-0.65) cases per million person-year. There was no statistically significant difference between the calendar year of disease onset (P = 0.97). The incidence rates were not significantly different between women and men (P = 0.63). Age was the main factor for the risk of CJD (P < 0.0001). Age-specific incidence rate increased after the age of 40 years with the peak being in the 70-79 years age group. Our data showed low annual incidence rate and high frequency of methionine homozygous prion protein genotype of sCJD in Taiwan. This report provided important epidemiological data on ethnic Chinese.

Fatal intoxication using amantadine and pramipexole in a uremic patient.

We report a fatal intoxication in a 59-year-old woman who had uremia undergoing hemodialysis, and then took amantadine and pramipexole for Parkinsonian tremor. Toxic manifestation includes myoclonus, ataxia, confusion and sudden death. This report highlights the fact that using amantadine and pramipexole may be fatal in patients with uremia even undergoing hemodialysis.

Efficacy of multivitamin supplementation containing vitamins B6 and B12 and folic acid as adjunctive treatment with a cholinesterase inhibitor in Alzheimer's disease: a 26-week, randomized, double-blind, placebo-controlled study in Taiwanese patients.

BACKGROUND: Elevated serum homocysteine levels have been associated with the development of Alzheimer's dementia (AD). The combined use of a mecobalamin capsule preparation, which contains vitamin B12 0.5 mg with an active methyl base, and an over-the-counter nutritional supplement that contains folic acid 1 mg and pyridoxine hyperchloride 5 mg may be effective as a homocysteine-lowering vitamin regimen. OBJECTIVE: The aim of this study was to determine whether oral multivitamin supplementation containing vitamins B6 and B12 and folic acid would improve cognitive function and reduce serum homocysteine levels in patients with mild to moderate AD. METHODS: This randomized, double-blind, placebocontrolled trial was conducted at En Chu Kong Hospital, Taipei, Taiwan. Male and female patients aged >50 years with mild to moderate AD and normal folic acid and vitamin B12 concentrations were enrolled. All patients received treatment with an acetylcholinesterase inhibitor and were randomized to receive add-on mecobalamin (B12) 500 mg + multivitamin supplement, or placebos, PO QD for 26 weeks. The multivitamin contained pyridoxine (B6) 5 mg, folic acid 1 mg, and other vitamins and iron. Serum homocysteine level was measured and cognitive tests were conducted at baseline and after 26 weeks. The primary efficacy outcome was change in cognition, measured as the change in score from baseline to week 26 on the Alzheimer's Disease Assessment Scale 11-item Cognition subscale. Secondary efficacy outcomes included changes in function in performance of activities of daily living (ADLs) and concentrations of homocysteine, B12, and folic acid. Tolerability was assessed by comparing the 2 study groups with respect to physical examination findings, including changes in vital signs, laboratory test abnormalities, concomitant medication use, and compliance of study medication was assessed using an interview with the patient's caregiver, as well as the monitoring of adverse events (AEs) throughout the study. RESULTS: Eighty-nine patients (45 men, 44 women; all Taiwanese; mean [SD] age, 75 [7.3] years) were enrolled and randomized. Overall, there were no significant differences in cognition or ADL function scores between the 2 groups. At week 26, the mean (SD) between-group difference in serum homocysteine concentration versus placebo was -2.25 (2.85) micromol/L (P = 0.008), and the mean serum concentrations of vitamin B12 and folic acid were significantly higher (but within normal range) in the multivitamin group compared with placebo (., +536.9 [694.4] pg/mL [P < 0.001] and +13.84 ng/mL [11.17] [P = 0.012] at 26 weeks, respectively). The 2 most common AEs were muscle pain (11.1% and 6.8%) and insomnia (8.9% and 9.1%) in the multivitamin and placebo groups, respectively. CONCLUSIONS: In this population of patients with mild to moderate AD in Taiwan, a multivitamin supplement containing vitamins B(6) and B(12) and folic acid for 26 weeks decreased homocysteine concentrations. No statistically significant beneficial effects on cognition or ADL function were found between multivitamin and placebo at 26 weeks.

Characterization of a familial case with primary erythromelalgia from Taiwan.

Familial primary erythromelalgia is a rare autosomal dominant disease characterized by redness and painful episodes of the feet and hands, which is often triggered by heat or exercise. In this report, a Taiwanese family with the characteristic features of erythromelalgia is described. Genetic linkage studies established that the disease locus maps to human chromosome 2. Sequence analysis indicated that the disease segregates with a novel mutation in the alpha subunit of the voltage-gated sodium channel (SCN9A or Na(v)1.7). The change observed is predicted to cause the substitution of a highly conserved isoluecine 136 for a valine within the first segment of the transmembrane domain (D1S1). Using immuno-histochemistry to stain a skin biopsy specimen from the affected region, we demonstrate that there is a significant reduction in the number of small fibers.

Effectiveness of vitamin B12 on diabetic neuropathy: systematic review of clinical controlled trials.

The clinical effectiveness of vitamin B12 and its active coenzyme form on diabetic neuropathy is uncertain. Therefore, we searched the English- and non-English-language literature on this topic by using MEDLINE (Ovid, PubMed), the Cochrane Controlled Trials Register, and related papers. We identified seven randomized controlled trials from June 1954 to July 2004 and reviewed them for the clinical effectiveness of vitamin B12 according to the following parameters: Measurement scales of somatic and autonomic symptoms or signs; vibrometer-detected thresholds of vibration perception; and, electrophysiologic measures such as nerve conduction velocities and evoked potentials. Three studies involved the use of vitamin B complex (including B12) as the active drug, and four used methylcobalamin. Two studies were of fairly good quality (Jadad score = 3/5), and five were of poor quality (Jadad score < or = 2/5). Both the vitamin B12 combination and pure methylcobalamin had beneficial effects on somatic symptoms, such as pain and paresthesia. In three studies, methylcobalamin therapy improved autonomic symptoms. Effects on vibration perception and electrophysiological measures were not consistent. With both the vitamin B12 combination and pure methylcobalamin, symptomatic relief was greater than changes in electrophysiological results. However, more high-quality, double-blind randomized controlled trials are needed to confirm the effects of vitamin B12 on diabetic neuropathy.

Transcranial color-coded sonography for the detection of middle cerebral artery stenosis.

OBJECTIVE: The purpose of this study was to validate the accuracy and criteria of transcranial color-coded sonography (TCCS) in detecting severe middle cerebral artery (MCA) stenosis. METHODS: One hundred ninety-three patients with acute ischemic cerebrovascular disease who received both TCCS and magnetic resonance angiography (MRA) examinations were evaluated. Middle cerebral artery stenosis assessed by MRA was graded as follows: grade 0, normal to mild (< 50%); grade 1, focal severe stenosis (> or = 50% and stenotic length within the M1 prebifurcation segment); and grade 2, diffuse severe stenosis (> or = 50% and stenotic length greater than the M1 prebifurcation segment). The peak systolic velocity (Vs) and mean velocity (Vm) of bilateral MCAs were obtained by TCCS. Estimates of sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for TCCS relative to MRA. RESULTS: After 46 patients were excluded, 309 MCAs (grade 0, 77.3%; grade 1, 15.5%; and grade 2, 7.1%) were evaluated. The optimal diagnostic accuracy of TCCS for the detection of grade 1 MCA stenosis can be reached if Vs is 140 cm/s or higher or Vm is 90 cm/s or higher (sensitivity, 83.3%; specificity, 91.2%). The optimal diagnostic accuracy of grade 2 MCA stenosis can be obtained if V(s) is lower than 50 cm/s or V(s) is 140 cm/s or higher (sensitivity, 81.8%; specificity, 92.1%). In our study, none of the grade 1 but around half of the grade 2 stenosis showed a low flow velocity pattern. CONCLUSIONS: Transcranial color-coded sonography is reliable in detecting severe MCA stenosis. Except for high flow velocity, the addition of a low cutoff of normal flow velocity in our criteria not only increases the study sensitivity but also enables the identification of around half of diffuse severe MCA stenosis.

Carotid duplex sonography in the follow-up of intracranial dural arteriovenous fistulae.

BACKGROUND AND PURPOSE: Studies to determine the value of noninvasive neurovascular studies for the effectiveness of treatment and long-term follow-up of dural arteriovenous fistulas (AVFs) are of clinical importance. We determined whether the serial changes of carotid duplex sonography (CDS) were correlated with the evolution of dural AVF status after treatment or follow-up. METHODS: Four parameters of CDS were studied in two groups of patients with dural AVF: resistance index, end diastolic velocity, peak systolic velocity, and flow volume of the external carotid artery (ECA). The first group included 13 patients who received endovascular therapy, the efficacy of which was determined by the results of postembolization angiography. In the second group, 16 patients received only clinical and CDS follow-up. Evolution of clinical symptoms was recorded and classified as deteriorating, stationary, or improving. Patients underwent CDS before and after treatment (group 1) or at long-term follow-up (group 2). RESULTS: In the first group, the resistance index of the ECA increased in patients with occluded or nearly occluded dural AVF after embolization (n = 7, P = .01), but it did not change significantly in patients with partial treatment (n = 6, P = .11). Of patients with occluded or nearly occluded dural AVF after embolization, the ECA resistance index increased in patients with noncavernous sinus dural AVF (n = 5, P = .003) but not in patients with cavernous sinus dural AVF (n = 2, P = .48). In the second group, CDS parameters-particularly the resistance index-were well correlated with clinical status during follow-up. CONCLUSION: The resistance index of the ECA is correlated with the effectiveness of treatment and clinical evolution of dural AVF.