A Case of Isolated Unilateral Glossopharyngeal Nerve Palsy.

Isolated palsy of the glossopharyngeal nerve is rare. We report the case of an elderly patient with unilateral right glossopharyngeal nerve palsy secondary to extra cranial ischemia. On examination there was no other deficit other than an absent right gag reflex. She was diagnosed clinically with ischemic stroke of the ninth nerve, and her daily dose of aspirin was increased from 81 mg to 325 mg. Magnetic resonance imaging of the brain showed a normal brainstem and cerebellum with patent intracranial circulation. Total resolution of the paralysis was seen 2 months later. The possible mechanisms suspected were diabetic or hypertensive stenosis of the vasa nervorum or compression of the ninth nerve by an internal carotid artery dissection or aneurysm. This article discusses the various etiologies and mechanisms of this rare condition. It is unique because of the nerve's location and relationship to other structures.

Identifying an Optimal Cutoff of the Montreal Cognitive Assessment to Predict Amyloid-PET Positivity in a Referral Memory Clinic.

BACKGROUND: Brain amyloid- positron emission tomography (PET) imaging is highly sensitive for identifying Alzheimer disease. Currently, there is a lack of insight on the association between amyloid-PET status and the widely used Montreal cognitive assessment (MoCA). Studying this relationship may optimize the clinical use of amyloid-PET imaging. OBJECTIVES: To evaluate the relationship between amyloid-PET status and MoCA scores and to identify a MoCA score cutoff that translates to amyloid-PET positivity. METHODS: Using retrospective chart review, patients from 2010 to 2017 with amyloid-PET scans (positive or negative) and MoCA test scores were included. We studied the relationship between amyloid-PET status and MoCA scores and the influence of age, sex, education, and race. A MoCA score cutoff for amyloid-PET positivity was estimated. RESULTS: Among the 684 clinic patients with dementia, 99 fulfilled inclusion criteria. Amyloid-PET positivity was associated significantly with lower MoCA scores (median=19, U=847, P=0.01). The MoCA score cutoff (25) used for minimal cognitive impairment (MCI) predicted amyloid-PET positivity suboptimally (sensitivity=94.6%, specificity=13.9%). A MoCA score cutoff of 20 patients had optimal sensitivity (64.2%) and specificity (67.4%). CONCLUSIONS: Amyloid-PET positivity is associated with lower MoCA scores. Clinical utility of amyloid-PET scan is likely to be suboptimal at the MoCA score cutoff for minimal cognitive impairment.

Endovascular Stroke Therapy Results Improve over Time: The 'Learning Curve' at a New Comprehensive Stoke Center.

BACKGROUND: The requirements for a comprehensive stroke center (CSC) include the capability to perform endovascular stroke therapy (EST). EST is a complex process requiring early identification of appropriate patients and effective delivery of intervention. In order to provide prompt intervention for stroke, CSCs have been established away from large academic centers in community-based hospitals. We hypothesized that quantifiable improvements would occur during the first 2 years of a community-based CSC as the processes and personnel evolved. We report the results over time of EST at a new community-based CSC. METHODS: We have retrospectively analyzed demographic data and outcome metrics of EST from the initiation phase of a new community-based CSC. Data was divided into year 1 and year 2. Statistical analysis (Student's t test and Fisher's exact test) was performed to compare the patient population and outcomes across the two time periods. Outcome variables included the thrombolysis in cerebral infarction (TICI) score, a change in the NIH stroke scale score and the modified Rankin Scale (mRS) score. Analysis of variance (ANOVA) was used to statistically analyze the relationship between population variables and outcome. Computed tomography (CT) angiography and CT perfusion analysis were used to select patients for EST. Approximately half of the patients undergoing EST were excluded from receiving intravenous recombinant tissue plasminogen activator (IV rt-PA) by standard criteria, while the other half showed no sign of improvement following 1 h of IV rt-PA treatment. Mechanical thrombolysis with a stentriever was performed in the majority of cases with or without intra-arterial medication. The majority of treated occlusions were in the middle cerebral artery. RESULTS: A total of 18 patients underwent EST during year 1 and year 2. A statistically significant increase in good outcomes (mRS score ≤2 at discharge) was seen from year 1 to year 2 (p = 0.05). There were trends towards faster interventions, decreased complications and mortality as well as an improved TICI score from year 1 to year 2. With ANOVA, mortality was statistically correlated with age (p = 0.06), while decreases in the NIH stroke scale (NIHSS) score following EST correlated with decreased mortality (p = 0.01). A higher TICI score was significantly associated with a decreased NIHSS score following EST (p = 0.01). CONCLUSIONS: At a new community-based CSC, improved outcome occurred from year 1 to year 2, and trends towards decreased mortality, fewer complications, and improved revascularization were observed. Furthermore, the data shows that improvement in NIHSS score after EST is associated with decreased mortality following stroke in this setting, implying a net benefit.

Strategies and outcomes for coiling very small aneurysms.

OBJECTIVE: Coiling of aneurysms 3 mm in diameter or less has been associated with a relatively high rate of complications, including iatrogenic rupture. The present study aimed to determine the clinical outcome of our technique for coiling small aneurysms. METHODS: A retrospective chart review was performed of prospectively collected data for all patients who had endovascular coiling of an aneurysm 3 mm in diameter or less between 2003 and 2008. Follow-up imaging with magnetic resonance or catheter angiography was performed at varying intervals after coiling, ranging from 1 to 6 years after the procedure. Angiographic results were assessed using the Raymond-Roy (RR) grading system. Clinical outcomes during the same period were measured using the modified Rankin Scale. RESULTS: Between March 2003 and April 2008, 20 patients underwent coil embolization of an aneurysm 3 mm or smaller--17 ruptured and 3 unruptured. After the procedure, 10 aneurysms were completely occluded (RR 1), 7 had residual filling of the neck (RR 2), and 3 had residual filling of the fundus (RR 3). There were no iatrogenic ruptures. Stent assistance was used in three cases. Balloon assistance was not used. Two patients were retreated, but no aneurysm reruptured. Clinical outcomes were as expected on the basis of the presenting Hunt & Hess grade. One patient with a ruptured aneurysm died from complications related to severe vasospasm. CONCLUSION: Aneurysms 3 mm in diameter or smaller can be coiled safely with the use of both bare platinum and hydrogel-coated coils. In most cases, coiling of small aneurysms can be performed without the use of adjunctive devices such as balloons or stents.

Dural arteriovenous fistulas: a review of the literature and a presentation of a single institution's experience.

OBJECTIVE: Dural arteriovenous fistulas (DAVFs) are arteriovenous shunts from a dural arterial supply to a dural venous channel, typically supplied by pachymeningeal arteries and located near a major venous sinus. A retrospective review was conducted to present the results of endovascular obliteration of DAVFs, with particular emphasis of newer liquid embolic agents, including Onyx-18 (MV3, Irvine, California, USA). METHODS: A review of the literature was performed, and a presentation of the number of treatments, complications, and outcomes is included here. The number of arterial embolizations and need for transvenous embolization, open surgery, and radiosurgery was assessed as well as normalization of retrograde cortical venous drainage. RESULTS: Thirty-nine patients (22 men and 17 women) underwent endovascular treatment of DAVFs at our institution from 2001 to 2009. Ages ranged from 39 to 71 years (mean, 48 years). Seventy-nine percent of patients had retrograde cortical venous drainage. The average number of embolizations in all patients was 2.1. Twelve patients underwent 40 embolization treatments with Onyx, with an obliteration rate of 75% and cortical venous drainage obliteration rate of 85%. Seventy-one percent (28/39) of patients had complete treatment of the fistula: 21 by purely endovascular treatment and 7 with endovascular therapy followed by craniotomy, as well as seven patients who underwent stereotactic radiosurgery after embolization. CONCLUSIONS: Endovascular management of DAVFs is a safe and effective method of treating these complex lesions.

Potential impact of amyloid imaging on diagnosis and intended management in patients with progressive cognitive decline.

Florbetapir F18 has been approved by the Food and Drug Administration for in vivo assessment of amyloid pathology in patients undergoing evaluation for Alzheimer disease (AD). The aim of this study was to determine the impact of amyloid imaging on the diagnoses and management of patients undergoing evaluation for cognitive decline. Patients were recruited to participate at 19 clinical sites. The site physician provided a provisional diagnosis, an estimate of their diagnostic confidence, and their plan for diagnostic evaluation and management both before and after receiving the results from amyloid imaging with florbetapir F18. Analyses compared the frequency of AD and non-AD diagnoses, plans for ancillary testing, and intended patient management before and after florbetapir imaging. A total of 229 patients participated in the trial (113 amyloid positive, 116 amyloid negative). After receiving the results of the florbetapir scan, diagnosis changed in 125/229, or 54.6% [95% confidence intervals (CI), 48.1%-60.9%], of cases, and diagnostic confidence increased by an average of 21.6% (95% CI, 18.3%-24.8%). A total of 199/229 or 86.9% (95% CI, 81.9%-90.7%) of cases had at least 1 change in their management plan. Intended cholinesterase inhibitor or memantine treatment increased by 17.7% (95% CI, 11.8%-25.8%) of all cases with positive scans and decreased by 23.3% (95% CI, 16.5%-31.8%) of all those with negative scans. Among subjects who had not yet undergone a completed work up, planned brain structural imaging (computed tomographic/magnetic resonance imaging) decreased by 24.4% (95% CI, 17.5%-32.8%) and planned neuropsychological testing decreased by 32.8% (95% CI, 25.0%-41.6%). In summary, amyloid imaging results altered physician's diagnostic thinking, intended testing, and management of patients undergoing evaluation for cognitive decline.

Statistics on BCS classification of generic drug products approved between 2000 and 2011 in the USA.

The Biopharmaceutics Classification system (BCS) classifies drug substances based on aqueous solubility and intestinal permeability. The objective of this study was to use the World Health Organization Model List of Essential Medicines to determine the distribution of BCS Class 1, 2, 3, and 4 drugs in Abbreviated New drug Applications (ANDA) submissions. To categorize solubility and intestinal permeability properties of generic drugs under development, we used a list of 61 drugs which were classified as BCS 1, 2, 3, and 4 drugs with certainty in the World Health Organization Model List of Essential Medicines. Applying this list to evaluation of 263 ANDA approvals of BCS drugs during the period of 2000 to 2011 indicated 110 approvals (41.8%) for Class 1 drugs (based on both biowaiver and in vivo bioequivalence studies), 55 (20.9%) approvals for Class 2 drugs, 98 (37.3%) approvals for Class 3 drugs, and no (0%) approvals for Class 4 drugs. The present data indicated a trend of more ANDA approvals of BCS Class 1 drugs than Class 3 or Class 2 drugs. Antiallergic drugs in Class 1, drugs for pain relief in Class 2 and antidiabetic drugs in Class 3 have received the largest number of approvals during this period.

Isolated unilateral hypoglossal nerve palsy due to vertebral artery dissection.

We report the case of a patient with unilateral tongue weakness secondary to an isolated lower motor neuron hypoglossal nerve palsy that was caused by a right vertebral artery dissection in the lower neck. The patient had a boggy tongue with a deviation to the right side but an otherwise normal neurological examination. Magnetic resonance angiography showed a narrow lumen of the right vertebral artery in the neck. After initially treating the patient with aspirin in the emergency room and later with warfarin for three months, there was complete recanalization of the right vertebral artery. Only one other case of vertebral artery dissection and twelfth nerve palsy has been reported before.

Clinical characterization of a kindred with a novel 12-octapeptide repeat insertion in the prion protein gene.

OBJECTIVE: To report the clinical, electroencephalographic, and neuroradiologic findings in a kindred with a novel insertion in the prion protein gene, PRNP. DESIGN: Clinical description of a kindred. SETTING: Mayo Clinic Alzheimer Disease Research Center (Rochester, Minnesota). SUBJECTS: Two pathologically confirmed cases and their relatives. MAIN OUTCOME MEASURES: Clinical features, electroencephalographic patterns, magnetic resonance imaging abnormalities, genetic analyses, and neuropathologic features. RESULTS: The proband was a woman with clinical and neuroimaging features of atypical frontotemporal dementia and ataxia. Generalized tonic-clonic seizures developed later in the disease course, and electroencephalography revealed spike and wave discharges but no periodic sharp-wave complexes. Her affected sister and father also exhibited frontotemporal dementia-like features, and both experienced generalized tonic-clonic seizures and gait ataxia late in the disease course. Genetic analyses in the proband identified a novel defect in PRNP, with 1 mutated allele carrying a 288-base pair insertion consisting of 12 octapeptide repeats. Neuropathologic examination of the proband and her sister revealed prion protein-positive plaques and widespread tau-positive tangles. CONCLUSIONS: This kindred has a unique combination of clinical and neuropathologic features associated with the largest base pair insertion identified to date in PRNP and underscores the need to consider familial prion disease in the differential diagnosis of a familial frontotemporal dementia-like syndrome.

Contrast stasis on noncontrast computed tomography as a predictor of stroke postthrombolysis.

Multimodal endovascular intervention is becoming more commonplace for the acute intervention of ischemic stroke. Hyperdensity in a portion of the treated territory is a common finding on postthrombolytic noncontrast CT (NCCT), but its significance is poorly understood. The authors conducted a single-institution, retrospective chart review of patients who had intraarterial thrombolysis of the anterior circulation between 2010 and 2011 with evidence of hyperdensity on NCCT following recanalization. Eighteen patients had evidence of postoperative contrast stasis causing hyperdensity on NCCT. One hundred percent of the patients had MR imaging evidence of completed strokes postoperatively in the same distribution as the stasis. Stasis on NCCT after intervention had a sensitivity and specificity of 82% and 0% for predicting stroke, respectively. Furthermore, the positive predictive value was 100%. The presence of contrast stasis on postthrombolytic NCCT correlates well with stroke seen on subsequent MR imaging.

Computed tomographic perfusion in assessing postoperative revascularization in moyamoya disease.

BACKGROUND: Our purpose in this study is to evaluate the use of computed tomographic perfusion (CTP) as an imaging modality to assess revascularization after superficial temporal artery (STA) to middle cerebral artery (MCA) bypass in patients with moyamoya disease. CASE DESCRIPTION: We present a series of 5 patients (mean age, 35; range, 20-50) with moyamoya disease who underwent STA-MCA bypass for ischemic stroke or transient ischemic attack (TIA). Preoperatively, all patients were evaluated with CTP; all showed clinically significant hypoperfusion in the MCA territory. All surgeries were performed by the senior author (ASB) and there were no periprocedural complications. Postoperative CTPs were performed to assess improvement after the bypass. The postoperative CTP images clearly demonstrated patency of the bypass and restoration of flow, particularly in the MCA distribution. At follow-up (mean, 18 months), 3 patients continued to be asymptomatic, one patient's hemiparesis improved, and another patient's hemiparesis improved but remained aphasic (mean Glasgow Outcome Score, GOS = 4.5). All displayed a reduced risk of recurrent stroke; no MCA strokes were observed. CONCLUSION: This study demonstrates that CTP, a more convenient and less expensive imaging test than other available options, can provide an assessment of cerebral blood flow after cerebral bypass that appears to correlate with postoperative clinical and angiographic findings. In addition, in this small series of moyamoya patients, STA-MCA bypass appeared to prevent recurrent TIAs and strokes.

Predicting cognitive decline and conversion to Alzheimer's disease in older adults using the NAB List Learning test.

To validate the Neuropsychological Assessment Battery (NAB) List Learning test as a predictor of future multi-domain cognitive decline and conversion to Alzheimer's disease (AD), participants from a longitudinal research registry at a national AD Center were, at baseline, assigned to one of three groups (control, mild cognitive impairment [MCI], or AD), based solely on a diagnostic algorithm for the NAB List Learning test (Gavett et al., 2009), and followed for 1-3 years. Rate of change on common neuropsychological tests and time to convert to a consensus diagnosis of AD were evaluated to test the hypothesis that these outcomes would differ between groups (AD>MCI>control). Hypotheses were tested using linear regression models (n = 251) and Cox proportional hazards models (n = 265). The AD group declined significantly more rapidly than controls on Mini-Mental Status Examination (MMSE), animal fluency, and Digit Symbol; and more rapidly than the MCI group on MMSE and Hooper Visual Organization Test. The MCI group declined more rapidly than controls on animal fluency and CERAD Trial 3. The MCI and AD groups had significantly shorter time to conversion to a consensus diagnosis of AD than controls. The predictive validity of the NAB List Learning algorithm makes it a clinically useful tool for the assessment of older adults.

Clock drawing test ratings by dementia specialists: interrater reliability and diagnostic accuracy.

The authors conducted a study of clock drawing test scoring by dementia specialists to determine interrater reliability and diagnostic accuracy. The authors randomly assigned 25 clocks from each of six predetermined groups based on consensus diagnosis (cognitive comparison subjects, subjects with a memory complaint but with normal neuropsychological testing, subjects with probable and possible mild cognitive impairment, and subjects with possible and probable Alzheimer's disease) to dementia specialists for blinded scoring using a binary yes/no impairment system and a 0-10 scale as subjectively determined by each individual clinician rater. The authors collapsed the six groups into three (comparison subjects, mild cognitive impairment patients, and Alzheimer's disease patients) and analyzed interrater reliability, sensitivity, and specificity for consensus diagnosis of mild cognitive impairment and Alzheimer's disease. The authors found excellent interrater reliability, sensitivity, and specificity for predicting consensus diagnosis. The 0-10 clock drawing test rating scale was more predictive of consensus diagnosis than the binary impairment scale. Based on rating systems, clock drawing test scoring by dementia clinicians had excellent interrater reliability and sensitivity for differentiating the mild Alzheimer's disease subjects from comparison subjects.

A new scale measuring psychologic impact of genetic susceptibility testing for Alzheimer disease.

This paper describes the development and psychometric properties of a new scale for assessing the psychologic impact of genetic susceptibility testing for Alzheimer disease (AD). The new instrument, The REVEAL Impact of Genetic Testing for Alzheimer's disease (IGT-AD) was designed to examine the unique nature of genetic information and the disease course of AD. The scale was tested as a part of a multicenter clinical trial designed to evaluate the impact of AD risk assessment and data were collected from 276 participants in the study. Using an iterative process of principal component analysis and Cronbach [alpha], the final 16-item IGT-AD was found to have a 2-factor structure with excellent internal reliability. Construct validity was established by patterns of correlation with other standardized self-reported measures. This scale should be useful in the identification of patients who maybe susceptible to the negative effects of receiving genetic information, monitoring of patients who have received genetic information, and as a tool for researchers who wish to study the effects of genetic susceptibility testing for AD.

Diagnostic utility of the NAB List Learning test in Alzheimer's disease and amnestic mild cognitive impairment.

Measures of episodic memory are often used to identify Alzheimer's disease (AD) and mild cognitive impairment (MCI). The Neuropsychological Assessment Battery (NAB) List Learning test is a promising tool for the memory assessment of older adults due to its simplicity of administration, good psychometric properties, equivalent forms, and extensive normative data. This study examined the diagnostic utility of the NAB List Learning test for differentiating cognitively healthy, MCI, and AD groups. One hundred fifty-three participants (age: range, 57-94 years; M = 74 years; SD, 8 years; sex: 61% women) were diagnosed by a multidisciplinary consensus team as cognitively normal, amnestic MCI (aMCI; single and multiple domain), or AD, independent of NAB List Learning performance. In univariate analyses, receiver operating characteristics curve analyses were conducted for four demographically-corrected NAB List Learning variables. Additionally, multivariate ordinal logistic regression and fivefold cross-validation was used to create and validate a predictive model based on demographic variables and NAB List Learning test raw scores. At optimal cutoff scores, univariate sensitivity values ranged from .58 to .92 and univariate specificity values ranged from .52 to .97. Multivariate ordinal regression produced a model that classified individuals with 80% accuracy and good predictive power. (JINS, 2009, 15, 121-129.).

Regulation of luteinizing hormone receptor mRNA expression by mevalonate kinase--role of the catalytic center in mRNA recognition.

We have shown that hormone-induced downregulation of luteinizing hormone receptor (LHR) in the ovary is post-transcriptionally regulated by an mRNA binding protein. This protein, later identified as mevalonate kinase (MVK), binds to the coding region of LHR mRNA, suppresses its translation, and the resulting ribonucleoprotein complex is targeted for degradation. Mutagenesis and crystallographic studies of rat MVK have established Ser146, Glu193, Asp204 and Lys13 as being crucial for its catalytic function. The present study examined the structural aspects of MVK required for LHR mRNA recognition and translational suppression. Single MVK mutants (S146A, E193Q, D204N and K13A) were overexpressed in 293T cells. Cytosolic fractions were examined for LHR mRNA binding activities by RNA electrophoretic mobility shift analysis. All the single MVK mutants showed decreased LHR mRNA binding activity compared with the wild-type MVK. Double mutants (S146A & E193Q, E193Q & D204N and E193Q & K13A) of MVK also showed a significant decrease in binding to LHR mRNA, suggesting that the residues required for catalytic function are also involved in LHR mRNA recognition. Mutation of the residues outside the catalytic site (D316A and S314A) did not cause any change in LHR mRNA binding activity of MVK when compared with wild-type MVK. To examine the biological effects of these mutants on LHR mRNA expression, a full-length capped rat LHR mRNA was synthesized and translated using a rabbit reticulocyte lysate system in the presence or absence of the MVK mutant proteins. The results showed that mutations of the active site residues of MVK abrogated the inhibitory effect on LHR mRNA translation. Therefore, these data indicate that an intact active site of MVK is required for its binding to rat LHR mRNA and for its translational suppressor function.

Ribonucleic acid binding protein-mediated regulation of luteinizing hormone receptor expression in granulosa cells: relationship to sterol metabolism.

Posttranscriptional mechanism plays a crucial role in regulating LH receptor (LHR) expression in the ovary. We have identified a novel trans-factor, LHR mRNA binding protein (LRBP), which binds to a polypyrimidine-rich bipartite sequence of the coding region of LHR mRNA, and its identity was established as mevalonate kinase (Mvk). Although an inverse relation between LHR mRNA expression and RNA binding activity of LRBP has been established, its intermediary role in LHR mRNA expression has not been demonstrated. The present study examined the direct role of Mvk in regulating LHR expression by using primary cultures of human granulosa cells as a model system. A marked decrease in LHR mRNA stability and an increase in Mvk expression were seen when cultured granulosa cells were treated with human chorionic gonadotropin (hCG) in vitro. This treatment also resulted in an increase in LHR mRNA binding activity in the cytosolic fractions prepared from hCG-treated cells compared with the control. Because Mvk expression is regulated by sterol response element-binding protein-1, which is sensitive to the cellular concentration of 25-hydroxycholesterol (25-OHC), cultured granulosa cells were treated with this oxysterol, and the expression of Mvk gene was examined. As expected, treatment with 25-OHC inhibited the Mvk (LRBP) expression, as well as the LHR mRNA binding activity of LRBP. To determine the role of Mvk in ligand-mediated down-regulation of LHR mRNA, cells were additionally treated with 25-OHC when treated with hCG. The results showed that the decrease in Mvk expression by oxysterol treatment abrogated ligand-induced down-regulation of LHR mRNA. These results therefore establish a direct participation of Mvk in regulating LHR expression and suggest a novel relationship between cholesterol metabolism and LHR expression in the ovary.

Regulation of luteinizing hormone receptor mRNA expression by a specific RNA binding protein in the ovary.

The expression of LH receptor mRNA shows significant changes during different physiological states of the ovary. Previous studies from our laboratory have identified a post-transcriptional mechanism by which LH receptor mRNA is regulated following preovulatory LH surge or in response to hCG administration. A specific binding protein, identified as mevalonate kinase, binds to the open reading frame of LH receptor mRNA. The protein binding site is localized to nucleotides 203-220 of the LH receptor mRNA and exhibits a high degree of specificity. The expression levels of the protein show an inverse relationship to the LH receptor mRNA levels. The hCG-induced down-regulation of LH receptor mRNA can be mimicked by increasing the intracellular levels of cyclic AMP by a phosphodiesterase inhibitor. An in vitro mRNA decay assay showed that addition of the binding protein to the decay system caused accelerated LH receptor mRNA decay. Our results therefore show that LH receptor mRNA expression in the ovary is regulated post-transcriptionally by altering the rate of mRNA degradation by a specific mRNA binding protein.

The role of luteinizing hormone/human chorionic gonadotropin receptor-specific mRNA binding protein in regulating receptor expression in human ovarian granulosa cells.

CONTEXT: In normally cycling women, LH receptor mRNA expression undergoes transient down-regulation after the LH surge. The same phenomenon is also seen during a hormonally induced ovarian cycle where the LH receptor mRNA expression is down-regulated in response to the administration of human chorionic gonadotropin (hCG). Although the granulosa cells isolated from the follicular aspirates at this stage show a decline in the expression of LH receptor mRNA, this diminished receptor expression returns to control levels upon culturing in serum-containing medium. OBJECTIVE: To understand the mechanism of hCG-induced loss of LH receptor mRNA expression, a cytosolic fraction (S100) was isolated from the granulosa cells, and its ability to bind LH receptor mRNA was assayed by performing RNA electrophoretic mobility gel shift analysis. RESULTS: The results showed that the mRNA binding activity of the S100 fraction was induced in the freshly isolated granulosa cells (d 1) from the follicular aspirates collected from women who had been injected with hCG to induce ovulation. The LH receptor mRNA expression in granulosa cells on d 1, as assessed by real-time PCR and Northern blot analysis, was significantly suppressed. Both the expression of LH receptor mRNA and RNA binding activity in the S100 fraction were then assessed after culturing granulosa cells for 4 d. The results showed that the LH receptor mRNA expression was significantly higher on d 4 compared with that seen on d 1. However, the RNA binding activity of the S100 fraction was significantly decreased on d 4 compared with that seen on d 1. These results show an increased association of RNA binding protein during LH receptor mRNA down-regulation. CONCLUSION: The present results support the notion that LH receptor mRNA expression in the human ovaries is regulated by an RNA binding protein.