Diffusion Tensor Imaging Mapping of Brain White Matter Pathology in Mitochondrial Optic Neuropathies

BACKGROUND AND PURPOSE:Brain white matter is frequently affected in mitochondrial diseases; optic atrophy gene 1-autosomal dominant optic atrophy and Leber hereditary optic neuropathy are the most frequent mitochondrial monosymptomatic optic neuropathies. In this observational study, brain white matter microstructure was characterized by DTI in patients with optic atrophy gene 1-autosomal dominant optic atrophy and Leber hereditary optic neuropathy, in relation to clinical and genetic features.MATERIALS AND METHODS:Nineteen patients with optic atrophy gene 1-autosomal dominant optic atrophy and 17 with Leber hereditary optic neuropathy older than 18 years of age, all genetically diagnosed, and 19 healthy volunteers underwent DTI by using a 1.5T MR imaging scanner and neurologic and ophthalmologic assessments. Brain white matter DTI metrics were calculated for all participants, and, in patients, their correlations with genetics and clinical findings were calculated.RESULTS:Compared with controls, patients with optic atrophy gene 1-autosomal dominant optic atrophy had an increased mean diffusivity in 29.2% of voxels analyzed within major white matter tracts distributed throughout the brain, while fractional anisotropy was reduced in 30.3% of voxels. For patients with Leber hereditary optic neuropathy, the proportion of altered voxels was only 0.5% and 5.5%, respectively, of which half was found within the optic radiation and 3.5%, in the smaller acoustic radiation. In almost all regions, fractional anisotropy diminished with age in patients with optic atrophy gene 1-autosomal dominant optic atrophy and correlated with average retinal nerve fiber layer thickness in several areas. Mean diffusivity increased in those with a missense mutation. Patients with Leber hereditary optic neuropathy taking idebenone had slightly milder changes.CONCLUSIONS:Patients with Leber hereditary optic neuropathy had preferential involvement of the optic and acoustic radiations, consistent with trans-synaptic degeneration, whereas patients with optic atrophy gene 1-autosomal dominant optic atrophy presented with widespread involvement suggestive of a multisystemic, possibly a congenital/developmental, disorder. White matter changes in Leber hereditary optic neuropathy and optic atrophy gene 1-autosomal dominant optic atrophy may be exploitable as biomarkers.

Mutations in optic atrophy gene 1 are the main cause of autosomal dominant optic atrophy (DOA) (Online Mendelian Inheritance in Man 605290).^1,2 DOA is characterized clinically by insidiously progressive visual loss in childhood, centrocecal scotoma, dyschromatopsia, and temporal or diffuse pallor of the optic discs, due to selective loss of retinal ganglion cells leading to atrophy of the optic nerve.^1,2 Similarly, Leber hereditary optic neuropathy (LHON) (Online Mendelian Inheritance in Man 535000) is characterized by subacute loss of central vision, dyschromatopsia, and optic atrophy due to maternally inherited point mutations in mitochondrial DNA that affect respiratory complex I.^1,2DOA and LHON represent the so-called nonsyndromic mitochondrial optic neuropathies, characterized by optic nerve atrophy as the only or at least prevalent pathologic feature with an early and preferential involvement of the small fibers in the papillomacular bundle.^3,4 Recent MR imaging studies by using voxel-based morphometry,⁵ DWI,⁶ and DTI⁷ have also indicated abnormalities of the optic radiation in patients with LHON, confirmed by postmortem investigation,⁶ suggesting a trans-synaptic degeneration. A similar secondary involvement of the retrogeniculate visual pathway could also be hypothesized in patients with DOA. Furthermore, given that the optic atrophy gene 1 (OPA1) is highly expressed in the retina but also in the brain^1,2,8 and that a subgroup of patients with specific OPA1 mutations have a multisystem neurologic disorder,⁹ it is reasonable to also hypothesize a subclinical extravisual brain involvement in patients with OPA1-DOA.The aim of the present study was to investigate the brain white matter of patients with OPA1-DOA compared with those with LHON and healthy controls, by using a voxelwise analysis of DTI, which can disclose abnormal water diffusivity in brain areas where atrophy and/or gliosis occur,¹⁰ to look for subtle structural alterations.     

Laparoscopic Radiofrequency Thermal Ablation for Uterine Adenomyosis

Background and Objectives:

Symptomatic uterine adenomyosis, unresponsive to medical therapy, is a challenging condition for patients who desire to preserve their uterus. This study was an evaluation of the feasibility and efficacy of laparoscopic radiofrequency thermal ablation of symptomatic nodular uterine adenomyosis.

Methods:

Fifteen women with symptomatic nodular adenomyosis, who had no plans for pregnancy but declined hysterectomy, underwent radiofrequency thermal ablation. Ultrasonography was performed at baseline and at postoperative follow-ups at 3, 6, 9, and 12 months. The impact of uterine adenomyosis–related symptoms was assessed according to the visual analog scale.

Results:

The median number of nodular lesions treated per patient was 1 (range, 1–2). The median baseline volume of the adenomyosis area was 60 cm³ (range, 18–128). The median reduction in volume was 32, 49.4, 59.6, and 65.4% at 3, 6, 9, and 12 months, respectively. A significant progressive improvement in the symptoms score was observed at the 4 follow-ups.

Conclusion:

In this study, laparoscopic radiofrequency thermal ablation reduced uterine adenomyosis–related symptoms and volume, with significant relief of symptoms.     

Failure of recombinant human interleukin-3 therapy to induce erythropoiesis in patients with refractory Diamond-Blackfan anemia [see comments]

In two previous studies, we observed that recombinant human interleukin- 3 (IL-3) induced an increase in marrow burst-forming unit-erythroid- derived colonies in vitro in some patients with Diamond-Blackfan anemia (DBA). To determine whether a similar erythropoietic response could be induced in vivo, we treated 13 patients with DBA (aged 4 to 19 years) with two preparations of IL-3. All patients had absent absolute reticulocyte counts and markedly reduced to absent recognizable bone marrow erythroid elements; patients with circulating reticulocytes in the previous 12 months were excluded from study. All patients except 1 had failed steroid therapy and had been transfusion-dependent since infancy; 1 patient was maintained on high-dose prednisone at the time of enrollment. On the first arm of the study, IL-3 (Immunex Corp, Seattle, WA) was administered subcutaneously using a dose escalation regimen of 125 to 500 micrograms/m2/day in divided dosage at 12-hour intervals, coadministered with 1.5 mg/kg/d of oral ferrous sulphate. Of the 13 patients that entered the trial, 4 stopped prematurely because of adverse side effects. In the other 9 evaluable cases, reticulocytes increased transiently in 1 patient from 0 to 65 x 10(9)/L after 35 days of IL-3 therapy at 250 micrograms/m2, but transfusion dependency persisted. One transient peak in absolute reticulocyte count was noted in 6 other patients, but no erythroid response was observed after completion of a full course of IL-3. Oral prednisone at 0.5 mg/kg/d was then coadministered with IL-3 at 500 micrograms/m2 to 5 of the patients without effect, and treatment was stopped. In 2 patients, a second preparation of IL-3 (Sandoz Canada Inc, Dorval, Quebec, Canada) was initiated in a dose escalation regimen of 2.5 to 10 micrograms/kg and was coadministered with ferrous sulphate. No erythroid response was observed in either patient, and in one of the two, alternate-day subcutaneous recombinant erythropoietin at 300 U/kg was administered for 3 weeks in combination with daily IL-3 at 10 micrograms/kg, but no increased erythropoiesis was seen. Significant increases in white blood cell and eosinophil counts during administration of both preparations of IL-3 were observed in all patients. These data show that the response of DBA patients to IL-3 in vivo is heterogeneous and cannot be predicted from in vitro studies. The absence of a corrective effect of IL-3 in these patients with DBA indicates that a deficiency of the cytokine is not central in the pathogenesis of the disorder.     

Robotic and Laparoscopic Surgery for Treatment of Colorectal Diseases

PURPOSE In the last ten years, several robotic systems have been developed to overcome the loss of the three-dimensional view and dexterity characteristic of laparoscopic surgery. The aim of this study was to compare the traditional laparoscopic approach and robotic techniques in the treatment of colorectal diseases.METHODS The study compares a consecutive series of patients treated surgically for colorectal disease from June 2001 to May 2003 with the da Vinci robotic system (Intuitive Surgical^®) and a matched number of patients who underwent conventional laparoscopy during the same time interval. The factors analyzed were the time required to prepare the patient and the room, total time of surgery, length of specimens, number of lymph nodes retrieved, blood loss, complications, and postoperative results.RESULTS The study included 106 patients (53 in each group). No differences were observed in total time of surgery (laparoscopic group, 222 ± 77 minutes vs. robotic group, 240 ± 61 minutes), specimen length (laparoscopic group, 29 ± 11 cm vs. robotic group, 27 ± 13 cm), or number of lymph nodes retrieved (laparoscopic group, 16 ± 9 vs. robotic group, 17 ± 10). It took significantly longer to prepare the operating room and patient in the robotic group (24 ± 12 minutes) than in the laparoscopic group (18 ± 7 minutes). There were three conversions to laparotomy in the laparoscopic group; in the robotic group, two cases were converted to laparoscopy and three to hand-assisted laparoscopy. No significant differences were observed between the two groups in terms of recovery of bowel function and postoperative hospital stay.CONCLUSIONS Robot-assisted surgery proved to be as safe and effective as laparoscopic techniques in the treatment of colorectal diseases. Because of its dexterity and three-dimensional view, the da Vinci system was particularly useful in specific stages of the procedure, e.g., takedown of the splenic flexure, dissection of a narrow pelvis, identification of nervous plexus, and handsewn anastomosis. The cost-effectiveness of the procedure still needs to be evaluated.     

Matrix‐assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS): peering into the cup of Jamshid

The complex process underlying the development of blood‐induced joint disease remains mysterious. Novel technologies such as matrix‐assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) to examine protein signatures may provide clues into the process.     

Panencephalopathic Creutzfeldt‐Jakob Disease with Distinct Pattern of Prion Protein Deposition in a Patient with D178N Mutation and Homozygosity for Valine at Codon 129 of the Prion Protein Gene

Prion diseases include sporadic, acquired and genetic forms linked to mutations of the prion protein (PrP) gene (PRNP). In subjects carrying the D178N PRNP mutation, distinct phenotypes can be observed, depending on the methionine/valine codon 129 polymorphism. We present here a 53‐year‐old woman with D178N mutation in the PRNP gene and homozygosity for valine at codon 129. The disease started at age 47 with memory deficits, progressive cognitive impairment and ataxia. The clinical picture slowly worsened to a state of akinetic mutism in about 2 years and the disease course was 6 years. The neuropathologic examination demonstrated severe diffuse cerebral atrophy with neuronal loss, spongiosis and marked myelin loss and tissue rarefaction in the hemispheric white matter, configuring panencephalopathic Creutzfeldt‐Jakob disease. PrP deposition was present in the cerebral cortex, basal ganglia and cerebellum with diffuse synaptic‐type pattern of immunoreactivity and clusters of countless, small PrP deposits, particularly evident in the lower cortical layers, in the striatum and in the molecular layer of the cerebellum. Western blot analysis showed the presence of type 1 PrP^Sc (Parchi classification). These findings underline the clear‐cut distinction between the neuropathological features of Creutzfeldt‐Jakob disease associated with D178N PRNP mutation and those of fatal familial insomnia.     

Acute alcoholic hepatitis,end stage alcoholic liver disease and liver transplantation: An Italian position statement

Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the “6-mo rule”. Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The “Group of Italian Regions” suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups.     

Synovial chondromatosis of the temporomandibular joint with glenoid fossa erosion: Disk preservation for spontaneous anatomical recovery

Synovial chondromatosis (SC) of the temporomandibular joint is a pseudoneoplastic condition characterized by benign cartilaginous metaplasia of synovial tissue mesenchymal residues with intra-articular nodule formation. TMJ involvement is rare. Interposition of loose bodies in the articular space can generate pressure, leading to glenoid fossa erosion with intracranial extension.The aim of this study was to present six SC cases with intracranial extension treated using a surgical procedure.All the patients were treated with open surgery. The superior compartment of the TMJ was opened widely to carefully remove the metaplasic mass. Temporal synovectomy was then performed. Attention was paid to preserving the integrity of the articular disc. The exposed dura mater was also preserved. No material was used to reconstruct the gap in the glenoid fossa.A 1-year follow-up showed no swelling or pain. Patients demonstrated good recovery of mouth opening, with improvement over previous mouth limitations. Morphological studies, performed using MRI and CT, showed complete anatomical recovery of the TMJ and total bone reconstruction of the glenoid fossa.Simple removal of intra-articular nodules, with TMJ arthroplasty and articular disk preservation, represents an efficient treatment option for full anatomical and functional recovery in synovial chondromatosis of the temporomandibular joint with glenoid fossa erosion of less than 1 cm².     

Prognosis and health-related quality of life in elderly patients after a mild to moderate trauma

The aims of this study were to compare outcome after a mild to moderate trauma in three subgroups of patients of increasing age (A1: <50, A2: 50–74, A3: >74 years) and to assess potential health-related quality of life (HRQOL) impairment. This is a follow-up study of a cohort of 418 trauma patients admitted to the High Dependency Unit of the Emergency Department of the University Hospital of Florence from July 2008 to February 2012. Six months after the event, a telephone interview using the Physical component summary (PCS) and Mental component summary (MCS) Health Composite Score (SF12) was conducted. Patients reported their QOL both at present and before trauma. In-hospital mortality was 10 of 418 (2.3 %); overall mortality was 27 of 244 (11 %) patients found at follow-up. No death was observed among A1 patients; overall mortality was (6/76) 7 % in A2 and (21/71) 30 % in A3 patients (p < 0.05 A1 vs A2, A1 vs A3 and A2 vs A3). Before the event, respectively, 94 and 96 % patients reported a normal MCS and PCS score (>39); after the event, the proportion of patients with a normal score value was significantly lower (MCS 70 %, p = 0.002; PCS 58 %, p < 0.0001). All subgroups showed a highly significant reduction in the scores’ value due to the trauma. After the event, the proportion of patients with normal scores was significantly lower (all p < 0.0001, except for MCS score in A1 subgroup, who showed p = 0.013) within all subgroups. Elderly patients’ prognosis was significantly worse compared with the younger counterpart; despite young patients’ optimal outcome, HRQOL was uniformly reduced across all age groups.