Gamma Knife stereotactic radiosurgery for idiopathic trigeminal neuralgia. Clinical article

Object
Trigeminal neuralgia pain causes severe disability. Stereotactic radiosurgery is the least invasive surgical option for patients with trigeminal neuralgia. Since different medical and surgical options have different rates of pain relief and morbidity, it is important to evaluate longer-term outcomes.

Methods
The authors retrospectively reviewed outcomes in 503 medically refractory patients with trigeminal neuralgia who underwent Gamma Knife surgery (GKS). The median patient age was 72 years (range 26–95 years). Prior surgery had failed in 205 patients (43%). The GKS typically was performed using MR imaging guidance, a single 4-mm isocenter, and a maximum dose of 80 Gy.

Results
Patients were evaluated for up to 16 years after GKS; 107 patients had > 5 years of follow-up. Eighty-nine percent of patients achieved initial pain relief that was adequate or better, with or without medications (Barrow Neurological Institute [BNI] Scores I–IIIb). Significant pain relief (BNI Scores I–IIIa) was achieved in 73% at 1 year, 65% at 2 years, and 41% at 5 years. Including Score IIIb (pain adequately controlled with medication), a BNI score of I–IIIb was found in 80% at 1 year, 71% at 3 years, 46% at 5 years, and 30% at 10 years. A faster initial pain response including adequate and some pain relief was seen in patients with trigeminal neuralgia without additional symptoms, patients without prior surgery, and patients with a pain duration of = 3 years. One hundred ninety-three (43%) of 450 patients who achieved initial pain relief reported some recurrent pain 3–144 months after initial relief (median 50 months). Factors associated with earlier pain recurrence that failed to maintain adequate or some pain relief were trigeminal neuralgia with additional symptoms and = 3 prior failed surgical procedures. Fifty-three patients (10.5%) developed new or increased subjective facial paresthesias or numbness and 1 developed deafferentation pain; these symptoms resolved in 17 patients. Those who developed sensory loss had better long-term pain control (78% at 5 years).

Conclusions
Gamma Knife surgery proved to be safe and effective in the treatment of medically refractory trigeminal neuralgia and is of value for initial or recurrent pain management. Despite the goal of minimizing sensory loss with this procedure, some sensory loss may improve long-term outcomes. Pain relapse is amenable to additional GKS or another procedure.

Incidence and risk factors for pulmonary exacerbation treatment failures in cystic fibrosis patients chronically infected with Pseudomonas aeruginosa

Background: Pulmonary exacerbations (PEx) are responsible for much of the morbidity and mortality associated with cystic fibrosis (CF). However, there is a paucity of data on outcomes in CF PEx and factors influencing outcomes.

Methods: We reviewed all PEx in patients infected with Pseudomonas aeruginosa treated with parenteral antibiotics over 4 years at our center. Treatment failures were categorized a priori as those PEx requiring antibiotic regimen change, prolongation of therapy > 20 days because of failure to respond, an early recurrent event within < 45 days, or failure to recover lung function to > 90% of baseline FEV1.

Results: A total of 101 patients were followed for 452 PEx. Treatment failures were observed in 125 (28%) of PEx; antibiotic regimen change was observed in 27 (6%), prolongation of therapy in 29 (6%), early recurrent events in 63 (14%), and failure to recover lung function to > 90% of baseline FEV1 in 66 (15%). Demographic factors associated with one or more treatment failures per year included advanced airways disease, use of enteric feeds, CF-related diabetes, and CF liver disease but did not include female sex or F508del homozygosity. Increased treatment failure risk was associated with lower admission FEV1 and increased markers of inflammation. At therapeutic completion, increased inflammatory markers correlated with treatment failure. Failure rates decreased with increasing number of active antimicrobial agents used based on in vitro susceptibility (zero, 28/65 [43%]; one, 38/140 [27%]; two, 59/245 [24%]; three, 0/2 [0%]; P = .02).

Conclusions: One-fourth of PEx fail to respond adequately to initial management. Patient demographic and episode-specific clinical information can be used to identify individuals at increased risk of initial management failure.

Synovial membrane immunohistology in early untreated juvenile idiopathic arthritis: differences between clinical subgroups

Abstract: Objective Juvenile idiopathic arthritis (JIA) consists of a heterogeneous group of inflammatory disorders, within which there are a number of clinical subgroups. Diagnosis and assignment to a particular subgroup can be problematical and more concise methods of subgroup classification are required. This study of the synovial membrane characterises the immunohistochemical features in early untreated, newly diagnosed JIA and compares findings with disease subgroup at 2 years.

Methods: 42 patients with newly diagnosed untreated JIA underwent synovial biopsy before the administration of steroids or disease-modifying antirheumatic drugs. Patients were classified as either polyarticular, persistent oligoarticular or extended-to-be oligoarticular. The location and semiquantitative analysis of T-cell subsets, B cells, macrophages and blood vessels were determined using immunohistochemistry.

Results: Synovial hyperplasia varied significantly between the three groups
(p<0.0001). There was a significant difference in the CD3 T-cell population between the three groups (p=0.004) and between the extended-to-be and persistent group (p=0.032). CD4 expression was significantly higher in the poly and extended-to-be oligo groups (p=0.002), again the extended-to-be group had more CD4 T cells than the persistent group (p=0.008). B-cell infiltrates were more marked in the polyarticular group and were significantly higher in the extended-to-be group compared with the persistent group (p=0.005). Vascularisation was more pronounced in the polyarticular and extended-to-be oligoarticular groups, the extended-to-be group had significantly more vascularisation than the persistent group (p=0.0002).

Conclusions: There are significant differences in the histomorphometric features of synovial tissue between patient subgroups. Immunohistological examination of synovial membrane biopsies may provide further insight into early disease processes in JIA.

Ankle disease in juvenile idiopathic arthritis: ultrasound findings in clinically swollen ankles

The ankle joint is frequently involved in juvenile idiopathic arthritis (JIA), but it is unclear whether this is predominantly due to synovitis, tenosynovitis, or both. We performed clinic-based ultrasound examination to assess the prevalence of synovitis and tenosynovitis in children with JIA felt clinically to have active inflammatory disease of the ankle.

A nonsynonymous LNK polymorphism associated with idiopathic erythrocytosis

Anemia is a symptom associated with cognitive dysfunction and is diagnosed if the hemoglobin level of a blood sample is too low. The clinical impact of chronically low hemoglobin level may be insuf?cient
brain oxygenation, which may result in a decline in cognitive functioning. Previous studies have provided evidence of decrements in cognitive functioning associated with anemia across various disease processes, but few have investigated the association between cognitive dysfunction and hemoglobin level in patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). As this population is inherently anemic, studying these patients allowed for an exploration of cognitive changes at mild, moderate, and severe levels of anemia. This investigation explored cutoff points for hemoglobin at which cognitive decline may occur. Findings showed decrements in cognitive functioning occurring at hemoglobin levels of 10 g/dL or below. Performance on measures of word retrieval, attention, and ?ne motor function was most affected which suggests fronto-temporal lobe dysfunction. Results provided evidence as to a hemoglobin cutoff point below which cognitive function may be affected in patients with AML and MDS. This cutoff value may provide a clinical marker at which cognitive testing and therapeutic interventions could be utilized to improve patients’ cognitive function, level of fatigue and overall quality of life.

Natural history of idiopathic erythrocytosis - A retrospective case series review

Idiopathic Erythrocytosis (IE) is a diagnosis given to patients who have an absolute erythrocytosis (red cell mass more than 25% above their mean normal predicted value) but who do not have a known form of primary or secondary erythrocytosis (BCSH guideline, 2005). We report here the results of a follow-up study of 80 patients (44 male and 36 female) diagnosed with IE from the United Kingdom and the Republic of Ireland over a 10 year period. Baseline information was initially collected when investigating for molecular causes of erythrocytosis in this group. The diagnosis of IE was made on the basis of a raised red cell mass >25% above mean normal predicted value, absence of Polycythaemia Vera (PV) based on the criteria of Pearson and Messinezy (1996), and the exclusion of secondary erythrocytosis (oxygen saturation >92% on pulse oximetry, no history of sleep apnoea, no renal or hepatic pathology, and a normal oxygen dissociation curve (if indicated). The average age at diagnosis of erythrocytosis was 34.5 (2–74 years). Erythropoietin levels were available for 77/80 of the patients and were low in 18 (23%) and normal or high in 59 (74%). Ultrasound imaging was carried out in 67 patients (84%) at time of diagnosis and no significant abnormalities found. Fourteen patients had a family history of erythrocytosis. These patients have now been followed up for an average of 9.4 years (range 1–39). Out of 80 patients 56 patients can still be classified as having IE, of whom 52 are living (cause of death in the other 4 - lung cancer, RTA, sepsis, unknown). Thirty-five of these patients are regularly venesected, 3 take hydroxyurea (one also venesected), 11 receive no treatment while treatment is unknown in 2. Twenty take aspirin, 1 warfarin and 31 no thromboprophylaxis. Four of these patients had suffered thromboembolic complications (3 with CVA/TIAs and 1 with recurrent DVT) at or before their original diagnosis. Since diagnosis 8 patients have had 9 thrombotic events of which 7 were arterial (1 CVA, 3 TIAs, 1 MI, 2 PVD) and 2 venous (DVT/PE). Twenty take aspirin, 1 dipyridamole, 1 warfarin and 30 take no thromboprophylaxis. Out of the 24 patients who now have a diagnosis other than IE, 8 have been diagnosed with myelo-proliferative disease. Thirteen patients have a molecular abnormality which is likely to account for their erythrocytosis (11 VHL, 1 PHD-2, 1 EPO-receptor mutations). Three patients have secondary erythrocytosis. Older case studies identified a heterogenous group of patients, some of whom probably had apparent erythrocytosis and some who had either primary polycythaemia or secondary causes later identified (Modan and Modan, Najean et al). More recent reviews have identified a more homogenous group with low rates of transformation to myelofibrosis/acute leukaemia and low rates of thrombosis of around 1% patient-year. Follow up of our initial patient group does indeed reveal a heterogeneous group of patients with 10% now diagnosed with an MPD, although when analysis is confined to those patients who continue to fulfil the criteria for IE, the clinical course has been more stable. There has been no progression to MDS or leukaemia in this group (one patient with PV progressed to AML). The rate of thrombosis is 1.6% patient-years which is lower than the rate seen in PV and is consistent with the rate identified in other series. Molecular defects continue to be identified in this group and future investigation is likely to reveal further abnormalities.