David F. Black

Novel mutations in the Na+, K+-ATPase pump gene ATP1A2 associated with familial hemiplegic migraine and benign familial infantile convulsions

Familial hemiplegic migraine (FHM) is a rare, severe, autosomal dominant subtype of migraine with aura. Up to 75% of FHM families have a mutation in the P/Q‐type calcium channel Cav2.1 subunit CACNA1A gene on chromosome 19p13. Some CACNA1A mutations also may cause epilepsy. Here, we describe novel missense mutations in the ATP1A2 Na+,K+‐ATPase pump gene on chromosome 1q23 in two families with FHM. The M731T mutation was found in a family with pure FHM. The R689Q mutation was identified in a family in which FHM and benign familial infantile convulsions partially cosegregate. In this family, all available affected family members with FHM, benign familial infantile convulsions, or both, carry the ATP1A2 mutation. Like FHM linked to 19p13, FHM linked to 1q23 also involves dysfunction of ion transportation and epilepsy is part of its phenotypic spectrum.

Identification of Intraarticular and Periarticular Uric Acid Crystals with Dual-Energy CT: Initial Evaluation

PURPOSE To estimate the accuracy, sensitivity, specificity, and interobserver agreement of dual-energy computed tomography (CT) in detection of uric acid crystals in joints or periarticular structures in patients with arthralgia and patients suspected of having gout, with joint aspiration results as reference standard. MATERIALS AND METHODS With institutional review board approval, patient consent, and HIPAA compliance, 94 patients (age range, 29-89 years) underwent dual-source, dual-energy (80 and 140 kVp) CT of a painful joint. A material decomposition algorithm was used to identify uric acid. Two blinded musculoskeletal radiologists evaluated the dual-energy CT images and classified the examination findings as positive or negative for the presence of uric acid crystals. Reference standard was the result of joint aspiration. RESULTS Forty-three of 94 patients (46%) underwent attempted joint aspiration within 1 month of dual-energy CT. Aspiration was successful in 31 of 43 patients (72%). In 12 of 31 patients (39%), uric acid crystals were identified at joint aspiration; in 19 patients, they were not. Readers 1 and 2 had no false-negative findings for uric acid at dual-energy CT. Sensitivity was 100% (12 of 12; 95% confidence interval (CI): 74%, 100%) for both readers. Specificity was 89% (17 of 19; 95% CI: 67%, 99% ) for reader 1 and 79% (15 of 19; 95% CI: 54%, 94%) for reader 2, with near-perfect agreement between the readers (κ = 0.87; range, 0.70-1.00) in the 31 patients who underwent aspiration. CONCLUSION Initial retrospective assessment suggests that dual-energy CT is a sensitive, noninvasive, and reproducible method for identifying uric acid deposits in joints and periarticular soft tissues in patients suspected of having gout.

Outcome of trigeminal nerve section in the treatment of chronic cluster headache

Chronic cluster headache accounts for 10 to 15% of all patients with cluster headache and is often resistant to medical management. The authors followed 17 patients with intractable chronic cluster headache who underwent trigeminal nerve section. They found that trigeminal nerve section is an effective treatment with acceptable morbidity for a carefully selected group of patients.

Failure of dabigatran and rivaroxaban to prevent thromboembolism in antiphospholipid syndrome: a case series of three patients.

Direct oral factor inhibitors (DOFIs) are an attractive alternative to vitamin K antagonists (VKA) for the treatment of patients with antiphospholipid syndrome (APS). In the absence of prospective, randomised trial data, reports of therapeutic failures in clinical practice alert clinicians to potential limitations of DOFI therapy for this indication. Data for all cases were collected from a centralised system that contains complete medical records of all patients treated and followed at Mayo Medical Center. We present here three consecutive APS patients who had had no thromboembolism recurrence on warfarin but were switched to DOFIs. The diagnosis of APS was established according to currently recommended criteria. The three cases were as follows: A woman with primary APS developed thrombotic endocarditis with symptomatic cerebral emboli after transition to dabigatran. A second woman with primary APS experienced ischemic arterial strokes and right transverse-sigmoid sinus thrombosis after conversion to rivaroxaban. A man with secondary APS suffered porto-mesenteric venous thrombosis after switching to rivaroxaban. None of these patients had failed warfarin prior to the transition to DOFIs. Based on these three cases, we advocate caution in using DOFIs for APS patients outside of a clinical trial setting, until further data becomes available.

Two de novo mutations in the Na,K-ATPase gene ATP1A2 associated with pure familial hemiplegic migraine

Familial hemiplegic migraine (FHM) is a rare autosomal dominantly inherited subtype of migraine, in which hemiparesis occurs during the aura. The majority of the families carry mutations in the CACNA1A gene on chromosome 19p13 (FHM1). About 20% of FHM families is linked to chromosome 1q23 (FHM2), and has mutations in the ATP1A2 gene, encoding the α2-subunit of the Na,K-ATPase. Mutation analysis in a Dutch and a Turkish family with pure FHM revealed two novel de novo missense mutations, R593W and V628M, respectively. Cellular survival assays support the hypothesis that both mutations are disease-causative. The identification of the first de novo mutations underscores beyond any doubt the involvement of the ATP1A2 gene in FHM2.

SMART: stroke-like migraine attacks after radiation therapy

We describe two adults with stroke-like migraine attacks after radiation therapy (SMART syndrome), propose revised diagnostic criteria, and review the previously reported patients. ‘SMART’ is an acronym for a newly recognized syndrome which occurs as a delayed consequence of cerebral irradiation and consists of prolonged, unilateral, migrainous neurological symptoms with transient, dramatic cortical gadolinium enhancement of the affected cerebral hemisphere and is sometimes punctuated by generalized seizures and ipsilateral EEG slowing. Although the neurological symptoms can last for weeks, full recovery occurs. An appropriate evaluation should exclude alternative explanations.

Cerebral venous sinus density on noncontrast CT correlates with hematocrit.

BACKGROUND AND PURPOSE: A positive correlation between HCT and CT attenuation of intravascular blood has long been assumed but has never been established by using substantial patient numbers and modern CT equipment. The purpose of this study was to determine whether apparent increased attenuation on CT in cerebral venous sinuses can be attributed to hemoconcentration alone and to assess whether sinus thrombosis can be differentiated from hemoconcentrated blood based on attenuation values alone. MATERIALS AND METHODS: We measured HUs in a region of interest within the confluence of dural venous sinuses in 166 unenhanced head CTs and correlated these data with HCT and HGB values in male and female patients aged 2 to 100 years. We then compared these data with similar measurements in 8 patients with recent venous sinus thrombosis. Two-tailed t test and linear regression analyses were performed to evaluate HGB and HCT between groups and with measured CT attenuation of intravascular blood, respectively. RESULTS: A statistically significant relationship was noted between both HCT and HGB with CT attenuation. Seven of 8 patients with sinus thrombosis had attenuation values >70, but none of the normal subjects had HUs >70. CONCLUSIONS: Hemoconcentration correlates with CT attenuation in cerebral venous sinuses. Our findings suggest that comparing the ratio of HUs to HCT may be useful in gauging concern for sinus thrombosis.

Imaging findings of migraine.

Increasingly sophisticated neuroimaging techniques have allowed researchers to begin to define functional and anatomical characteristics of migraine. This paper reviews current knowledge and techniques employed. Assessing present‐day knowledge limitations it concludes that with parallel advances in the technology of imaging and the pathophysiologic understanding of migraine, a reliable biomarker may be discovered in the future.

Stroke-Like Migraine Attacks after Radiation Therapy (SMART) Syndrome Is Not Always Completely Reversible: A Case Series

Clinical and imaging findings in 11 patients with SMART syndrome were reviewed. All patients became symptomatic on average 20 years postirradiation and all showed unilateral gyriform cerebral enhancement that resolved spontaneously in 2–5 weeks though 45% had residual neurologic deficits. Twenty-seven percent of patients developed laminar necrosis and brain biopsies of 4 patients showed nonspecific findings. SUMMARY: We retrospectively reviewed clinical and imaging findings in 11 patients with stroke-like migraine attacks after radiation therapy (SMART) syndrome to better understand this disorder previously thought to be reversible. Six men and 5 women had complex bouts of neurologic impairment beginning, on average, 20 years after cerebral irradiation. All had characteristic, unilateral gyriform enhancement on MR imaging that developed within 2–7 days and typically resolved in 2–5 weeks. Unlike prior reports, 45% had incomplete neurologic recovery manifesting as dysphasia, cognitive impairment, or hemiparesis. The remaining 55% recovered completely over an average of 2 months. Three of 11 patients developed cortical laminar necrosis. Brain biopsies in 4 of 11 did not demonstrate a specific pathologic substrate. These additional 11 patients contribute to the understanding of variability in stroke-like migraine attacks after radiation therapy syndrome, which often but not uniformly manifests with headaches and seizures, demonstrates a typical evolution of imaging findings, and may result in permanent neurologic and imaging sequelae.

Decreasing Incidence of Cluster Headache: A Population‐Based Study in Olmsted County, Minnesota

The incidence of medically recognized cluster headache within Olmsted County, Minnesota, from 1989 through 1990, was determined by using modified International Headache Society criteria. The results were compared with previously published incidence data from 1979 through 1981. The overall age‐ and sex‐adjusted incidence decreased from 9.8/100,000 person‐years in 1979–1981 to 2.07/100,000 person‐years in 1989–1990.