Rostral anterior cingulate volume predicts treatment response to cognitive-behavioural therapy for posttraumatic stress disorder

OBJECTIVE: To index the extent to which treatment response in posttraumatic stress disorder (PTSD) is predicted by rostral anterior cingulate cortex (rACC) volume. METHOD: We used structural magnetic resonance imaging in a 1.5 T scanner to examine subjects with PTSD (n = 13), traumatized control subjects (n = 13) and nontraumatized control subjects (n = 13). Subjects with PTSD then participated in 8 sessions of cognitive-behavioural therapy, after which we reassessed them for PTSD. RESULTS: According to voxel-based morphometry, treatment responders had larger rACC volume than nonresponders. Further, symptom reduction was associated with larger rACC volume. CONCLUSION: Consistent with evidence for the neural bases of extinction learning, PTSD patients with larger rACC volume may be better able to regulate fear during cognitive-behavioural therapy and thus achieve greater treatment gains.     

Age-related changes of the ciliary muscle in comparison with changes induced by treatment with prostaglandin F2 alpha. An ultrastructural study in rhesus and cynomolgus monkeys

The relationship between individual ciliary muscle cells and the surrounding connective tissue was studied in the eyes of three normal, young (3-4 years) cynomolgus monkeys (Macaca fascicularis), three aged (34-36 years) rhesus monkeys (Macaca mulatta) and seven young (3-7 years) cynomolgus monkeys topically treated with prostaglandin F2 alpha (PGF2 alpha) for 4-8 days. In normal eyes, collagen fibrils and microfibrils are in places in continuity with the muscle cells' basal lamina, which is connected to the cell membrane by fine fibrillous material. In old eyes, the basal lamina is markedly thickened, masking the connection of fibrils with the muscle cells' membrane. A distinctive finding in several muscle cells of old eyes are electronlucent clefts, 60-80 nm wide, between basal lamina and cell membrane, which are not transversed by fibrils or fibrillous material. The cell membrane of these muscle cells shows large folds filled with disarranged myofilaments. Additionally, these cells contain inclusion bodies consisting of concentrically arranged double membranes. Following treatment with PGF2 alpha, similar changes are seen in young animals, too. Here, the muscle cells have lost their connection to the extracellular fibrils due to a PGF2 alpha-induced lysis of extracellular material. Lack of attachment between basal lamina and altered muscle cells in aged eyes might indicate an involvement of the extracellular matrix in age-related changes of the individual ciliary muscle cells.     

ACR Appropriateness Criteria on Acute Shoulder Pain

The shoulder joint is a complex array of muscles, tendons, and capsuloligamentous structures that has the greatest freedom of motion of any joint in the body. Acute (<2 weeks) shoulder pain can be attributable to structures related to the glenohumeral articulation and joint capsule, rotator cuff, acromioclavicular joint, and scapula. The foundation for investigation of acute shoulder pain is radiography. Magnetic resonance imaging is the procedure of choice for the evaluation of occult fractures and the shoulder soft tissues. Ultrasound, with appropriate local expertise, is an excellent evaluation of the rotator cuff, long head of the biceps tendon, and interventional procedures. Fluoroscopy is an excellent modality to guide interventional procedures. Computed tomography is an excellent modality for characterizing complex shoulder fractures. Computed tomographic arthrography or fluoroscopic arthrography may be alternatives in patients for whom MR arthrography is contraindicated. A multimodal approach may be required to accurately assess shoulder pathology. The ACR Appropriateness Criteria(?) are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.     

Chromosome aberrations determined by sFISH and G-banding in lymphocytes from workers with internal deposits of plutonium

Purpose: To examine the influence of α-particle radiation exposure from internally deposited plutonium on chromosome aberration frequencies in peripheral blood lymphocytes of workers from the Sellafield nuclear facility, UK. Materials and methods: Chromosome aberration data from historical single colour fluorescence in situ hybridization (sFISH) and Giemsa banding (G-banding) analyses, together with more recent sFISH results, were assessed using common aberration analysis criteria and revised radiation dosimetry. The combined sFISH group comprised 29 men with a mean internal red bone marrow dose of 21.0 mGy and a mean external γ-ray dose of 541 mGy. The G-banding group comprised 23 men with a mean internal red bone marrow dose of 23.0 mGy and a mean external γ-ray dose of 315 mGy. Results: Observed translocation frequencies corresponded to expectations based on age and external γ-ray dose with no need to postulate a contribution from α-particle irradiation of the red bone marrow by internally deposited plutonium. Frequencies of stable cells with complex aberrations, including insertions, were similar to those in a group of controls and a group of workers with external radiation exposure only, who were studied concurrently. In a similar comparison there is some suggestion of an increase in cells with unstable complex aberrations and this may reflect recent direct exposure to circulating lymphocytes. Conclusions: Reference to in vitro dose response data for the induction of stable aberrant cells by α-particle irradiation indicates that the low red bone marrow α-particle radiation doses received by the Sellafield workers would not result in a discernible increase in translocations, thus supporting the in vivo findings. Therefore, the greater risk from occupational radiation exposure of the bone marrow resulting in viable chromosomally aberrant cells comes from, in general, much larger γ-ray exposure in comparison to α-particle exposure from plutonium.     

Cerebral Perfusion Pressure is Maintained in Acute Intracerebral Hemorrhage: A CT Perfusion Study

BACKGROUND AND PURPOSE:Although blood pressure reduction has been postulated to result in a fall in cerebral perfusion pressure in patients with intracerebral hemorrhage, the latter is rarely measured. We assessed regional cerebral perfusion pressure in patients with intracerebral hemorrhage by using CT perfusion source data.MATERIALS AND METHODS:Patients with acute primary intracerebral hemorrhage were randomized to target systolic blood pressures of <150 mm Hg (n = 37) or <180 mm Hg (n = 36). Regional maps of cerebral blood flow, cerebral perfusion pressure, and cerebrovascular resistance were generated by using CT perfusion source data, obtained 2 hours after randomization.RESULTS:Perihematoma cerebral blood flow (38.7 ± 11.9 mL/100 g/min) was reduced relative to contralateral regions (44.1 ± 11.1 mL/100 g/min, P = .001), but cerebral perfusion pressure was not (14.4 ± 4.6 minutes⁻¹ versus 14.3 ± 4.8 minutes⁻¹, P = .93). Perihematoma cerebrovascular resistance (0.34 ± 0.11 g/mL) was higher than that in the contralateral region (0.30 ± 0.10 g/mL, P < .001). Ipsilateral and contralateral cerebral perfusion pressure in the external (15.0 ± 4.6 versus 15.6 ± 5.3 minutes⁻¹, P = .15) and internal (15.0 ± 4.8 versus 15.0 ± 4.8 minutes⁻¹, P = .90) borderzone regions were all similar. Borderzone cerebral perfusion pressure was similar to mean global cerebral perfusion pressure (14.7 ± 4.7 minutes⁻¹, P ≥ .29). Perihematoma cerebral perfusion pressure did not differ between blood pressure treatment groups (13.9 ± 5.5 minutes⁻¹ versus 14.8 ± 3.4 minutes⁻¹, P = .38) or vary with mean arterial pressure (r = −0.08, [−0.10, 0.05]).CONCLUSIONS:Perihematoma cerebral perfusion pressure is maintained despite increased cerebrovascular resistance and reduced cerebral blood flow. Aggressive antihypertensive therapy does not affect perihematoma or borderzone cerebral perfusion pressure. Maintenance of cerebral perfusion pressure provides physiologic support for the safety of blood pressure reduction in intracerebral hemorrhage.

Patients with intracerebral hemorrhage (ICH) most often present with elevated blood pressure (BP), but acute treatment remains controversial.^1,2 Despite the results of recent randomized controlled trials of BP management demonstrating no excess of adverse clinical events,^3,4 many physicians are reluctant to aggressively use antihypertensive agents in the acute phase of ICH. This relucence is primarily based on persisting theoretic concerns that there is a zone of tissue at risk for ischemic injury surrounding the acute hematoma.⁵ In addition, more recent MR imaging studies have suggested that subacute ischemic injury occurs in areas remote from the hematoma, including borderzone (BZ, also known as watershed) regions.^6–11 The etiology of these ischemic injuries has been postulated to be hemodynamic compromise secondary to BP reduction.¹⁰ Studies of CBF in the perihematoma region indicate that this region is relatively hypoperfused, but not severely enough to result in ischemia.^12–14 Previous PET studies have demonstrated that the perihematoma region is, in fact, hypometabolic, likely secondary to the primary brain injury, and that the oxygen extraction fraction is not elevated, indicating the absence of misery perfusion.^12,15 Nonetheless, it is possible that reduction of BP will result in a fall in cerebral perfusion pressure (CPP), subsequently precipitating ischemia.¹⁶ In the Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial (ICH ADAPT), we demonstrated that acute BP reduction is not associated with a significant fall in CBF.¹⁷ It has been demonstrated, however, that CPP is more sensitive than CBF or CBV to changes in blood pressure.¹⁸ The relationship between CPP and BP reduction in patients with intracerebral hemorrhage is unknown.Global CPP is normally calculated as the difference between the mean arterial pressure and intracranial pressure, which requires insertion of an intraventricular manometer. Monitoring of intracranial pressure and CPP is generally reserved for patients with a decreased level of consciousness and/or obstructive hydrocephalus requiring ventricular drainage. In these cases, current consensus guidelines recommend that BP be titrated to ensure that CPP is between 50 and 70 mm Hg.^19,20 In addition, global CPP may not reflect local variations in intracranial pressure due to the mass effect of a hematoma, particularly in small hematomas.²¹ Measurements of regional CPP might inform clinical BP management decisions. With PET, it has been demonstrated that CPP can be calculated as a ratio of CBF to CBV.¹⁸ We adapted this technique by using CTP source data from ICH ADAPT to assess local CPP in acute ICH. We tested the hypothesis that aggressive antihypertensive therapy reduces CPP in the perihematoma and borderzone regions.     

Clinical and neurophysiologic features of progressive myoclonus epilepsy without renal failure caused by SCARB2 mutations

Purpose: Mutations of the SCARB2 gene cause action myoclonus renal failure syndrome (AMRF), a rare condition that combines progressive myoclonus epilepsy (PME) with severe renal dysfunction. We describe the clinical and neurophysiologic features of PME associated with SCARB2 mutations without renal impairment. Methods: Clinical and neurophysiologic investigations, including wakefulness and sleep electroencephalography (EEG), polygraphic recording (with jerk‐locked back‐averaging and analysis of the EEG–EMG (electromyography) relationship by coherence spectra and phase calculation), multimodal evoked potentials, and electromyography were performed on five Italian patients with SCARB2 mutations. Key Findings: The main clinical features were adolescent–young adulthood onset, progressive action myoclonus, ataxia, absence of cognitive deterioration and, in most cases, epilepsy. The severity of the epilepsy could vary from uncontrolled seizures and status epilepticus in patients with adolescent onset to absent or rare seizures in patients with adult onset. Relevant neurophysiologic findings were a pronounced photosensitivity and massive action myoclonus associated with rhythmic myoclonic jerks at a frequency of 12–20 Hz, clinically resembling a postural tremor. The cortical origin of rhythmic myoclonus was demonstrated mainly by coherence and phase analysis of EEG–EMG signals indicating a significant EEG–EMG coupling and a direct corticospinal transfer. Significance: Our patients with SCARB2 mutations showed the clinical and neurophysiologic phenotype of PME, in which epilepsy could be extremely severe, extending the spectrum reported in the typical AMRF syndrome. Patients with PME of unknown origin of adolescent or young adult onset, with these neurophysiologic features, should be tested for SCARB2 mutations, even in the absence of renal impairment.     

Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy with brain malformations

We recently identified DEPDC5 as the gene for familial focal epilepsy with variable foci and found mutations in >10% of small families with nonlesional focal epilepsy. Here we show that DEPDC5 mutations are associated with both lesional and nonlesional epilepsies, even within the same family. DEPDC5‐associated malformations include bottom‐of‐the‐sulcus dysplasia (3 members from 2 families), and focal band heterotopia (1 individual). DEPDC5 negatively regulates the mammalian target of rapamycin (mTOR) pathway, which plays a key role in cell growth. The clinicoradiological phenotypes associated with DEPDC5 mutations share features with the archetypal mTORopathy, tuberous sclerosis, raising the possibility of therapies targeted to this pathway. Ann Neurol 2014;75:782–787     

Interfacility transport of patients admitted to the ICU: perceived needs of family members

INTRODUCTION: Limited research has been published regarding the needs of immediate family members with respect to the transport of critically ill loved ones. Furthermore, very little information exists on transport teams members' perception of the needs of the family members. METHODS: During a 9-month period, a 25-item questionnaire was given to family members of adult patients who were transported by air or ground. All patients were admitted into an adult intensive care unit at a major university teaching hospital. Family members were asked to rank the relative importance of each item with regard to informational or situational needs. The identical questionnaire was given to the critical care transport teams employed by the hospital. The team members were asked to indicate what they thought the family members ranked as important. RESULTS: Forty-two of 100 family members (42%) returned the questionnaire by mail. All 13 (100%) critical care transport team members completed surveys as well. Statistical comparisons indicated that family members and team members differed significantly on 13 of 25 items. Team members generally underestimated the importance of these items to family members. CONCLUSION: These findings suggest that, in this sample, transporting crew members often misperceived family members informational and situational needs.