Resistance to thyroid hormone-beta co-existing with partially empty sella in a Jordanian male.

Resistance to thyroid hormone-beta (RTHbeta) is a rare inherited syndrome characterized by variable reduced tissue responsiveness to the intracellular action of triiodothyronine (T3), the active form of the thyroid hormone. The presentation of RTHbeta is quite variable and mutations in the thyroid hormone receptor beta (THR-B) gene have been detected in up to 90% of patients. The proband was a 34-year-old Jordanian male who presented with intermittent palpitations. His thyroid function tests (TFTs) showed a discordant profile with high free T4 (FT4) at 45.7 pmol/L (normal: 12-22), high free T3 (FT3) at 11.8 pmol/L (normal: 3.1-6.8) and inappropriately normal TSH at 3.19 mIU/L (normal: 0.27-4.2). Work up has confirmed normal alpha subunit of TSH of 0.1 ng/mL (normal <0.5) and pituitary MRI showed no evidence of a pituitary adenoma; however, there was an interesting coincidental finding of partially empty sella. RTHbeta was suspected and genetic testing confirmed a known mutation in the THR-B gene, where a heterozygous A to G base change substitutes valine for methionine at codon 310. Screening the immediate family revealed that the eldest son (5 years old) also has discordant thyroid function profile consistent with RTHbeta and genetic testing confirmed the same M310V mutation that his father harbored. Moreover, the 5-year-old son had hyperactivity, impulsivity and aggressive behavior consistent with attention deficit hyperactivity disorder (ADHD). This case demonstrates an unusual co-existence of RTHbeta and partially empty sella in the same patient which, to our knowledge, has not been reported before. Learning points: We report the coincidental occurrence of RTHbeta and a partially empty sella in the same patient that has not been previously reported. TFTs should be done in all children who present with symptoms suggestive of ADHD as RTHbeta is a common finding in these children. The management of children with ADHD and RTHbeta could be challenging for both pediatricians and parents and the administration of T3 with close monitoring may be helpful in some cases. Incidental pituitary abnormalities do exist in patients with RTHbeta, although extremely rare, and should be evaluated thoroughly and separately.

Pronounced reduction of acquisition of conditioned eyeblink responses in young adults with focal cerebellar lesions impedes conclusions on the role of the cerebellum in extinction and savings.

Human cerebellar lesion studies provide good evidence that the cerebellum contributes to the acquisition of classically conditioned eyeblink responses (CRs). As yet, only one study used more advanced methods of lesion-symptom (or lesion-behavior) mapping to investigate which cerebellar areas are involved in CR acquisition in humans. Likewise, comparatively few studies investigated the contribution of the human cerebellum to CR extinction and savings. In this present study, young adults with focal cerebellar disease were tested. A subset of participants was expected to acquire enough conditioned responses to allow the investigation of extinction and saving effects. 19 participants with chronic surgical lesions of the cerebellum and 19 matched control subjects were tested. In all cerebellar subjects benign tumors of the cerebellum had been surgically removed. Eyeblink conditioning was performed using a standard short delay protocol. An initial unpaired control phase was followed by an acquisition phase, an extinction phase and a subsequent reacquisition phase. Structural 3T magnetic resonance images of the brain were acquired on the day of testing. Cerebellar lesions were normalized using methods optimized for the cerebellum. Subtraction analysis and Liebermeister tests were used to perform lesion-symptom mapping. As expected, CR acquisition was significantly reduced in cerebellar subjects compared to controls. Reduced CR acquisition was significantly more likely in participants with lesions of lobule VI and Crus I extending into Crus II (p<0.05, Liebermeister test). Cerebellar subjects could be subdivided into two groups: a smaller group (n=5) which showed acquisition, extinction and savings within the normal range; and a larger group (n=14) which did not show acquisition. In the latter, no conclusions on extinction or savings could be drawn. Previous findings were confirmed that circumscribed areas in lobule VI and Crus I are of major importance in CR acquisition. In addition, the present data suggest that if the critical regions of the cerebellar cortex are lesioned, the ability to acquire CRs is not only reduced but abolished. Subjects with lesions outside these critical areas, on the other hand show preserved acquisition, extinction and saving effects. As a consequence, studies in human subjects with cerebellar lesions do not allow drawing conclusions on CR extinction and savings. In light of the present findings, previous reports of reduced extinction in humans with circumscribed cerebellar disease need to be critically reevaluated.

Benefit of second catheter angiography in patients with nontraumatic subarachnoidal hemorrhage.

PURPOSE: This study aimed to determine the yield of repetitive catheter angiography (digital subtraction angiography (DSA)) for the detection of causative vascular lesions in patients with nontraumatic subarachnoidal hemorrhage (SAH) and negative initial DSA. We hypothesize that a second DSA might be helpful to detect an initially occult bleeding source. METHODS: We retrospectively evaluated 649 patients with acute SAH and invasive catheter angiographies between 2004 and 2012. In 90 SAH patients initial imaging was negative concerning a causative bleeding source. A total of 113 repetitive DSA were performed. Two neuroradiologists reanalyzed the initial imaging and the result of the reangiography independently. RESULTS: In 4/90 patients (4.5 %) bleeding source was first detected in the second or third DSA. In all other patients, no causative vascular lesion was found. Reasons for the initially false negative diagnostics were one dissecting aneurysm and thrombosis of three aneurysms within the acute phase of SAH. CONCLUSIONS: Repetitive DSA revealed the cause of SAH in 4.5 % of the cases. These findings have a therapeutic and prognostic impact. We think that at least a second DSA should be part of diagnostic work-up in patients with SAH and missing bleeding source, even considering the risk of an additional invasive angiography itself.

The impact of user fee removal policies on household out-of-pocket spending: evidence against the inverse equity hypothesis from a population based study in Burkina Faso.

BACKGROUND: User fee removal policies have been extensively evaluated in relation to their impact on access to care, but rarely, and mostly poorly, in relation to their impact on household out-of-pocket (OOP) spending. This paucity of evidence is surprising given that reduction in household economic burden is an explicit aim for such policies. Our study assessed the equity impact on household OOP spending for facility-based delivery of the user fee reduction policy implemented in Burkina Faso since 2007 (i.e., subsidised price set at 900 Communauté Financière Africaine francs (CFA) for all, but free for the poorest). Taking into account the challenges linked to implementing exemption policies, we aimed to test the hypothesis that the user fee reduction policy had favoured the least poor more than the poor. METHODS: We used data from six consecutive rounds (2006-2011) of a household survey conducted in the Nouna Health District. Primary outcomes are the proportion of households being fully exempted (the poorest 20% according to the policy) and the actual level of household OOP spending on facility-based delivery. The estimation of the effects relied on a Heckman selection model. This allowed us to estimate changes in OOP spending across socio-economic strata given changes in service utilisation produced by the policy. FINDINGS: A total of 2,316 women reported a delivery between 2006 and 2011. Average household OOP spending decreased from 3,827 CFA in 2006 to 1,523 in 2011, without significant differences across socio-economic strata, neither in terms of households being fully exempted from payment nor in terms of the amount paid. Payment remained regressive and substantially higher than the stipulated 900 CFA. CONCLUSIONS: The Burkinabè policy led to a significant and sustained reduction in household OOP health spending across all socio-economic groups, but failed to properly target the poorest by ensuring a progressive payment system.

A novel CASR mutation associated with neonatal severe hyperparathyroidism transmitted as an autosomal recessive disorder.

BACKGROUND: Neonatal severe primary hyperparathyroidism (NSHPT, MIM 239200) is most often an isolated disorder that is due to biallelic inactivating mutations in the CASR, the gene encoding the calcium sensing receptor; NSHPT is inherited from parents with familial hypocalciuric hypercalcemia, each of whom has one mutated CASR allele. OBJECTIVES: To report clinical and genetic findings in a brother and sister with NSHPT due to a novel mutation in the CASR transmitted as an autosomal recessive trait and to examine the functional effect of the mutation. SUBJECTS AND METHODS: A brother and sister with marked hypercalcemia due to NSHPT were identified; the boy also had craniosynostosis requiring surgical repair. The genotyping of the CASR in both children and their parents who were eucalcemic and normophosphatemic was undertaken. In order to examine the significance of the variant CASR identified, the CASR variant was expressed in vitro and examined by three computer computational programs [PolyPhen2, MutationTaster, Sorting Intolerant From Tolerant (SIFT)] designed to evaluate the effect of a nucleotide variant on the structure and likely functional consequence upon the protein product. RESULTS: A sequence variant in the CASR was identified [G>T point mutation at nucleotide c.2303 in exon 7 (c.2303G>T) resulting in the replacement of glycine by valine at codon 768 (p.Gly768Val)]. Two copies of this CASR variant were present in the genome of the siblings while a single copy of the CASR variant was present in both of the clinically and biochemically normal parents, a pattern of transmission consistent with autosomal recessive inheritance of NSHPT in this family. When expressed in HEK293 cells in vitro, the novel Gly768Val variant did not interfere with protein generation or migration to the cell membrane in vitro. The analysis of the functional effect of the Gly768Val CASR variant by the PolyPhen2, MutationTaster, and Sorting Intolerant From Tolerant computer programs revealed that this mutation was very likely to be deleterious. CONCLUSION: The NSHPT associated with biallelic Gly768Val mutations of the CASR in two siblings with severe hypercalcemia and hyperparathyroidism and their clinically and biochemically normal heterozygous parents was transmitted as an autosomal recessive disorder in this family.

3D Rotational Angiography After Non-Traumatic SAH.

PURPOSE: In about 15 % of patients with SAH no causative vascular lesions can be found in acute imaging with CTA and DSA. Usually, repeat DSA is mandatory and bears the usual risk of invasive angiography. The present study attempts to assess the diagnostic impact of 3 D rotational angiography in order to avoid repeat DSA. MATERIALS AND METHODS: From January 2004 to December 2012, 649 patients with an acute non-traumatic SAH were examined. 91 patients with negative initial imaging diagnostics concerning the bleeding source were included in this study. These patients underwent a second angiography scan: 61 in 4-plane technique, and 30 with 2-plane technique and additional 3 D DSA. Two cohorts were compared: patients with repeat angiography in conventional 4-plane technique from 2004 to July 2008 and 2-plane technique with additional 3 D rotational DSA from 2008 to 2012. Statistical significance was verified by means of Fisher's exact test. RESULTS: In the second DSA scan, 4 aneurysms in 4 patients (4/91; 4.4 %) were found and treated subsequently. Within the first 4.5 years of this study, 401 patients with SAH were treated and 61 of them underwent repeat angiography (15.2 %) compared to 30 of 248 patients (12.1 %) in the last 4.5 years of this study. In the first group we found 3 aneurysms during repeat angiography, and in the second group we found 1. No significance was reached (p = 0.29) but there was a tendency towards higher diagnostic security using 3D-DSA. CONCLUSION: Using 3 D rotational DSA in initial imaging workup might help to reduce false-negative results concerning the bleeding source of acute SAH. At least because of this fact, 3 D rotational DSA should be part of the diagnostic workup after acute SAH.

The role of decompressive craniectomy in children with severe traumatic brain injury.

OBJECTIVE: Severe traumatic brain injury (TBI) remains the leading cause of death in children. The present study analyses the outcome of children after severe TBI treated by decompressive craniectomy (DC) due to elevated intracranial pressure (ICP) in a single centre. METHODS: Fifty-six consecutive children (age < 16 years) were treated for severe TBI at our institution between 2001 and 2011. For study purposes, children with severe generalized traumatic brain swelling without concomitant mass lesion were further analysed. Descriptive statistics were used to report clinical conditions as well as outcome measurements after conservative treatment only in comparison to secondary decompressive craniectomy. RESULTS: Of 56 children, a total of eight children presented with generalized and progressive traumatic brain swelling and impending brain herniation. Four children were treated conservatively following standardized local protocol for anti-oedematous management, with ICP amenable to intensified therapy. Four children required decompressive surgery due to progressive oedema refractory to intensified conservative management. Children receiving secondary DC had a longer stay in the intensive care unit as well as a longer average time of assisted ventilation compared to children treated conservatively. Concomitant injuries were more severe in the DC subgroup. Yet, Glasgow Outcome Scale was equally distributed in both groups. CONCLUSION: In children with refractory ICP conditions due to severe TBI, decompressive surgery might lead to a similar favourable outcome compared to children in whom ICP can be controlled only by conservative management. Timing of surgery depends on the neurological deterioration of the patients and a continuous ICP monitoring.

[Reangiography after perimesencephalic subarachnoid hemorrhage]. / Reangiographie nach perimesenzephaler Subarachnoidalblutung.

BACKGROUND: This study aimed to determine the value of digital subtraction angiography (DSA) for the detection of causative vascular lesions in patients with perimesencephalic subarachnoid hemorrhage (SAH) after initially negative noninvasive and invasive neurovascular imaging, such as computed tomography angiography (CTA), DSA and magnetic resonance angiography (MRA). MATERIALS AND METHODS: We analyzed the value of repeated DSA for the detection of causative vascular lesions in 750 patients presenting to our institution with SAH and including 30 with a purely perimesencephalic pattern of subarachnoidal hemorrhage and initially negative noninvasive and invasive neurovascular imaging over a 10-year period. RESULTS: Repeated DSA demonstrated a causative vascular lesion in 1 patient (3.3%) but no causative vascular lesions were detected in the other patients. CONCLUSIONS: Repeated DSA can be used to detect a source of hemorrhage after initially negative imaging diagnostics in some rare cases. Such a finding has a therapeutic and prognostic impact especially for aneurysms in the posterior circulation which bear a higher risk of renewed hemorrhaging. Therefore, we believe that repeated DSA should be recommended in patients with perimesencephalic SAH even under consideration of the risk of complications caused by a second invasive DSA.

Occipital nerve stimulation for the treatment of chronic cluster headache - lessons learned from 18 months experience.

OBJECTIVE: Neuromodulation has been recognized as a valuable surgical treatment option for patients with refractory chronic cluster headache (CCH). Due to the small number of afflicted individuals, the knowledge about this specific therapy is limited. In this study, we present our experiences with bilateral occipital nerve stimulation (ONS) in patients with CCH focusing on patient selection, pre- and postoperative evaluation, surgical procedures, and outcome. PATIENTS AND METHODS: Since December 2008, 10 patients with CCH have been treated with ONS at our department. Patients were recruited and clinically followed by a neurologist and a neurosurgeon. Baseline data records on frequency, intensity, and duration of attacks as well as the use of medication were assessed with a 30-day diary. Standardized questionnaires were used pre- and postoperatively and during the follow-up on a regular basis. Surgical procedure and stimulation parameters were standardized for all patients. Lead implantation was followed by a test period of 30 days prior to implantation of the permanent generator. Mean follow-up time was 12 months (range 3-18). RESULTS: All patients responded to the stimulation treatment. Frequency, duration, and severity of the cluster attacks were reduced in 90% of the patients. One patient had a significant reduction of his concomitant tension headache. 70 % of the patients needed less medication during the attacks. All patients reported an improvement in their quality of life. The SF-36 showed a tendency toward objective improvement in the field of psychological comfort. As a major adverse event, one generator had to be exchanged due to a local infection. Another patient had to be reoperated due to a scar tissue formation around the thoracic connector. CONCLUSIONS: ONS is a valuable tool in the treatment of patients with refractory CCH. According to our data, the potential side effects and complication rates of the operation are small. With a meticulous selection of patients by an interdisciplinary team, CCH can bed improve in the majority of the patients. Yet, the optimal parameters for the stimulation regarding pulse width and frequency remain unclear. For this reason, we started a prospective single-center observational trial at our center in October 2009, including patients with ONS, to identify the best stimulation parameters.

[Reliability of a measurement technique to characterise standing properties and to quantify balance capabilities of healthy subjects on an unstable oscillatory platform (Posturomed)]. / Zuverlässigkeitsprüfung eines Messverfahrens zur Charakterisierung des Standverhaltens und Quantifizierung des Balancevermögens auf einer instabilen Plattform (Posturomed).

INTRODUCTION: Specific sensomotoric training is recommended to improve walking dysfunctions, prevent injurious falls or improve the reaction capacities of athletes. The oscillatory Posturomed platform can be used as a simple measuring procedure to characterise balance ability. Standard values for the one legged stance or test-retest reliability are unknown. METHOD: 55 healthy subjects (37 +/- 15 years) were tested during one legged stance on the unstable Posturomed platform. We recorded the total path of the platform in mm as balance recovery movements (BRM) as well as the ratio of failed attempts. To evaluate Test-Retest-Reliability, 12 subjects were retested one month later. RESULTS: To maintain balance, healthy subjects required twice as many BRM in anterior-posterior (AP) direction (40.7 +/- 26 mm) as in medio-lateral (ML) (17.4 +/- 8 mm). 8 % of the recorded attempts were counted as failed attempts due to subjects' unstable standing. On average, subjects required 15.5 +/- 18 mm less BMR when standing on their stronger leg than on the other leg. Younger subjects (25 +/- 2 y) required less BMR than older (59 +/- 11 y) subjects (49.2 versus 64.7 mm, p = 0.006). Subjects with a high level of physical training required less BMR. Test-Retest measurements showed an average difference of 3.9 +/- 6.1 mm. DISCUSSION: The Posturomed Platform can be used to evaluate stance ability and characterise the patterns of one legged stance. The measurements are reproducible, but include a small learning effect. Further studies including EMG could provide more understanding of neuromuscular control mechanisms and their adaption to training.