Transient Clinical Improvement Research Articles

PReS-FINAL-2086: In vitro investigation of the sustained therapeutic effect of etanercept loaded microspheres on human rheumatoid arthritis fibroblast-like synoviocytes

Anti-TNFα treatment has become an important part of our systemic treatment in chronic inflammatory arthritis. Local application to the joint produces transient clinical improvement since the drug quickly leaves the joint.

A Rare Cause of Cardiac Tamponade: Hypereosinophilic Syndrome

We describe a male adult patient who presented with chest discomfort and shortness of breath. A diagnosis of cardiac tamponade was made by transthoracic echocardiogram. Urgent pericardiocentesis was performed and analysis of pericardial fluid showed presence of eosinophil. Complete blood picture showed peripheral eosinphilia as well. Subsequent work up for eosinophilia showed ova of Clonorchis sinesis from the stool thus a course of praziquantel was given. Transient clinical improvement and lowering of eosinophil count were observed but two weeks later he developed acute coronary syndrome. Urgent coronary angiogram showed coronary vasospasm. Endomyocardial biopsy was performed afterwards which showed marked eosinophilic infiltrate. Bone marrow biopsy and skin biopsy showed marked marrow eosinophilia and leucocytoclastic vasculitis with abundant eosinophils, respectively. A diagnosis of hypereosinophilic syndrome was made after exclusion of secondary and clonal eosinophilia. After oral steroid was given, his condition was stabilized and the eosinophil count was normalized.

P4‐334: Imaging resolution and transient clinical improvement following cyclophosphamide treatment of a cerebral amyloid angiopathy‐related lesion

P4‐334: Imaging resolution and transient clinical improvement following cyclophosphamide treatment of a cerebral amyloid angiopathy‐related lesion

A case with coincidental diagnosis of primary central nervous system lymphoma and lymph node sarcoidosis

Primary central nervous system lymphoma (PCNSL) is rare. Clinical and histological differential diagnosis of systemic lymphoma and sarcoidosis continues to be a challenge. The first case report in the German and English literature of PCNSL and synchronous sarcoidosis is presented. Synchronous mediastinal lymphadenopathy suggestive of non-Hodgkin's lymphoma (NHL) or sarcoidosis was noted. Both conditions require alternative therapeutic and prognostic considerations to PCNSL. A regime of intrathecal and adjuvant systemic chemotherapy led to transient clinical improvement prior to the patient's demise through overwhelming sepsis and multiorgan failure. Post mortem findings confirmed synchronous PCNSL with mediastinal lymph node sarcoidosis.

Lymphocytic Hypophysitis: Differential Diagnosis and Effects of High-Dose Pulse Steroids, Followed by Azathioprine, on the Pituitary Mass and Endocrine Abnormalities — Report of a Case and Literature Review

We report on a man with a progressively increasing pituitary mass, as demonstrated by MRI. It produced neurological and ophthalmological symptoms, and, ultimately, hypopituitarism. MRI also showed enlargement of the pituitary stalk and a dural tail phenomenon. An increased titer of antipituitary antibodies (1:16) was detected in the serum. Pituitary biopsy showed autoimmune hypophysitis (AH). Neither methylprednisolone pulse therapy nor a subsequent treatment with azathioprine were successful in recovering pituitary function, or in inducing a significant reduction of the pituitary mass after an initial, transient clinical and neuroradiological improvement. Anterior pituitary function evaluation revealed persistent hypopituitarism. AH is a relatively rare condition, particularly in males, but it represents an emerging entity in the diagnostic management of pituitary masses. This case shows that response to appropriate therapy for hypophysitis may not be very favorable and confirms that diagnostic management of nonsecreting pituitary masses can be a challenge. Clinical, imaging, and laboratory findings are useful for suggesting the diagnosis, but pituitary biopsy may be necessary to confirm it.

Transkranielle Magnetstimulation zur Behandlung von Bewegungsstörungen

Diese Arbeit gibt einen Überblick über den therapeutischen Einsatz der repetitiven transkraniellen Magnetstimulation (rTMS) bei Patienten mit Bewegungsstörungen. Die meisten Studien untersuchten die therapeutischen Effekte der rTMS beim Morbus Parkinson. Zunächst wurde hier der akute Effekt einer einmaligen rTMS-Anwendung über dem primären motorischen Kortex (M1) auf die Bradykinese und andere Parkinsonsymptome untersucht. Die rTMS erfolgte meist nach kurzzeitigem Absetzen der vorbestehenden dopaminergen Medikation. Mehrere interventionelle Studien zeigten, dass eine erregbarkeitssteigernde, hochfrequente (≥5 Hz) rTMS des M1 kurzzeitig die motorische Symptomatik bessert, insbesondere wenn mehr als 1 000 Stimuli verabreicht werden. In neueren Studien wurde die rTMS mehrfach an unterschiedlichen Tagen verabreicht und mehrere kortikale Zielareale in einer Sitzung stimuliert. Hierdurch ließ sich der günstige Effekt einer hochfrequenten rTMS auf die Parkinsonsymptome verlängern. Bei Patienten mit fokaler Handdystonie, medikamentös induzierten Dyskinesien, essenziellem Tremor, Chorea oder Tics wurden bislang vor allem die therapeutischen Effekte einer hemmenden, niederfrequenten (1 Hz) rTMS untersucht. In Abhängigkeit von der Bewegungsstörung und dem Reizort zeigte sich nach 1 Hz rTMS eine kurzzeitige Besserung der klinischen Symptome. Trotz dieser ermutigenden Resultate ist die interventionelle rTMS bei Patienten mit Bewegungsstörungen immer noch als ein experimentelles Therapieverfahren einzustufen. Die Hindernisse, welche einem breiten therapeutischen Einsatz der rTMS bei Patienten mit Bewegungsstörungen im Wege stehen, werden diskutiert.

Aphasic or amnesic status epilepticus detected on PET but not EEG

To describe five patients with ictal aphasia and one patient with ictal amnesia, who had focal positron emission tomography (PET) hypermetabolism but no clear ictal activity on electroencephalography (EEG). (18)F-Fluorodeoxyglucose (FDG)-PET scans with concomitant EEG were obtained in five patients with suspected ictal aphasia or ictal amnesia without ictal activity on EEG. We reviewed medical history, EEG, imaging data, and treatment outcome. Brain magnetic resonance imaging (MRI) showed no structural abnormalities in any of the patients. EEG showed left temporal irregular delta activity in three patients, with aphasia and nonspecific abnormalities in two other patients, all without clear ictal pattern. All patients demonstrated focal hypermetabolism on PET scan. The hypermetabolism was in the left frontotemporal region in patients with ictal aphasia and in the bilateral hippocampal region in the patient with amnesia. Three patients who received intravenous benzodiazepines during their episodes had transient clinical improvement. With antiepileptic drug (AED) treatment, symptoms gradually resolved in all patients. Concomitant resolution of PET hypermetabolism was documented in three patients who had follow up scans. One patient with ictal aphasia later developed recurrent episodes, each with recurrent PET hypermetabolism. This patient and one other patient required immune-modulating therapy in addition to AEDs. FDG-PET imaging should be considered as a diagnostic tool in patients with suspected ictal aphasia or amnesia, who fail to show clear evidence of ictal activity on EEG.

Fatal outcome of pylephlebitis treated with transhepatic percutaneous drainage

Pylephlebitis, also called suppurative endophlebitis of the portal vein, is a rare potentially life-threatening acute abdominal complication of an intra-abdominal inflammatory process. Only early recognition substantially reduces the catastrophic mortality. As its clinical picture is fairly nonspecific, radiological findings, while not pathognomonic, are of great use in early diagnosis and management of these patients. We report a rare case of pylephlebitis with no identified intraperitoneal septic process in a 75-year-old man. Diagnosis was suspected on imaging features and confirmed with percutaneous transhepatic needle puncture. Thereafter, a drainage catheter was placed into the intrahepatic portal system. After a transient clinical improvement during the three following days, the drainage stopped and the patient developed a septic shock requiring transfer to intensive care but he died approximately 24 h later.

Lumbar subcutaneous shunt: a novel technique for therapeutic decision making in normal pressure hydrocephalus (NPH) and benign intracranial hypertension (BIH)

Selecting patients who will benefit from a permanent CSF diversion procedure in benign intracranial hypertension (BIH) or communicating hydrocephalus due to normal pressure hydrocephalus (NPH) has inherent problems. The percutaneous introduction of a lumbar subcutaneous shunt (LSS) under local anaesthesia facilitates both a prolonged CSF drainage under aseptic conditions and also elicits an adequate clinical response. We describe the technique of a lumbar subcutaneous shunt and our experience with its use in patients with BIH and NPH. Postprocedure changes in the patients' clinical status were noted. Patients with a transient clinical improvement underwent a subsequent definitive CSF diversion; those with a sustained clinical improvement or no change in symptoms had no further procedure.

Effect of single mannitol bolus in intracerebral hemorrhage

Because of existing controversy about use of mannitol in intracerebral hemorrhage (ICH) this open exploratory trial with blinded outcome assessment of single mannitol bolus in ICH was undertaken. CT proven primary supratentorial ICH patients having midline shift of > or =3 mm were randomized into 20% mannitol (1.5 g/kg) and control groups. Clinical evaluation included Glasgow coma scale (GCS) score, Canadian Neurological scale (CNS) score, pupils, breathing, extensor posturing and contra-lateral pyramidal signs. On cranial MRI horizontal (HS), superior sagittal sinus to pontomesencephalic junction (SSS-PMJ) distance and edema hematoma complex were measured. Twelve patients each were in mannitol and control groups. The age, sex, GCS score, CNS score, pupillary asymmetry, contra-lateral pyramidal signs, HS and SSS-PMJ distance in mannitol and control groups did not differ significantly. Mannitol infusion resulted clinical improvement in five patients, which lasted for 30-60 min. HS and SSS-PMJ distance in mannitol and control groups did not change at 30 or 60 min from the baseline. The change in HS and SSS-PMJ distance were also not significantly different between the two groups both at 30 and 60 min. Mannitol led to transient clinical improvement in five patients without significant reduction in HS or SSS-PMJ distance at 30 and 60 min.

Neuroleptic Malignant Syndrome

Neuroleptic Malignant Syndrome

Secondary sclerosing cholangitis after long-term treatment in an Intensive care unit: clinical presentation, endoscopic findings, treatment, and follow-up

We present ten patients who developed secondary sclerosing cholangitis following long-term treatment in an intensive care unit (ICU) between 1999 and 2004. Ten consecutive patients who had no evidence suggestive of pre-existing hepatobiliary disease were admitted to an ICU because of trauma (n = 5), intracerebral hemorrhage (n = 3), or nonabdominal postsurgical complications (n = 2). All the patients had required treatment with long-term ventilation, catecholamines, total parenteral nutrition, and several antimicrobial agents. Cholestasis was first noted within 11 days after the initial insult. Endoscopic retrograde cholangiopancreatography (ERCP), performed after a median follow-up of 69 days, revealed multifocal stricturing and beading of the intrahepatic bile ducts, and attenuation of the peripheral branches. In all the patients, the bile ducts were partially filled by black-pigmented thrombotic material. All the patients underwent endotherapy, which comprised sphincterotomy and removal of the occluding material, in an attempt to improve biliary drainage; the treatment had to be repeated in seven of the ten patients. After a median follow-up period of 21 months, despite transient clinical improvement following endotherapy, complete recovery has not been achieved in any of the patients and so far one patient has had to undergo orthotopic liver transplantation as a result of end-stage liver disease. The development of secondary sclerosing cholangitis in patients who have received long-term treatment in an ICU is a rare event of unknown pathophysiology, but patients demonstrate characteristic findings on ERCP. It is not known whether endotherapy can delay the progress of the condition in the long term.

Brief Communication: Sirolimus-Associated Pneumonitis: 24 Cases in Renal Transplant Recipients

Interstitial pneumonitis is an ill-defined side effect of sirolimus, a new immunosuppressant drug recently introduced for patients having organ transplantation. To evaluate clinical and laboratory features of sirolimus-associated pneumonitis. Case series. 1 transplantation center in Paris, France. 24 patients who had renal transplantation and developed sirolimus-associated pneumonitis, including 8 patients previously reported. Symptoms; laboratory tests, including bronchoalveolar fluid analysis; and computed tomography (CT) of the chest. Withdrawal or dose reduction of sirolimus. Clinical symptoms included cough (23 patients), fatigue (20 patients), fever (16 patients), and dyspnea (8 patients). Computed tomography of the chest showed reticular and ground-glass opacities (4 patients), bronchiolitis obliterans-organizing pneumonia (19 patients), and lobar consolidation (1 patient). Bronchoalveolar lavage showed lymphocytic (19 patients) or eosinophilic (3 patients) alveolitis or pulmonary hemorrhage (2 patients). A reduction in the sirolimus dose resulted in transient clinical improvement in 2 patients, but discontinuation of drug therapy was eventually necessary in all patients. All patients recovered completely within 6 months. The sirolimus trough level in patients from this single center was higher than that usually used in patients having renal transplantation. Lymphocytic alveolitis and radiologic bronchiolitis obliterans-organizing pneumonia are the key findings in sirolimus-associated pneumonitis. Sirolimus withdrawal was associated with recovery within 6 months.

Thalamic ependymal cyst presenting with tremor

We report the case of a 6-year-old boy presenting with intention tremor. CT and MR scanning showed a large thalamic cyst. Stereotactic tapping of this cyst was carried out as the first step in surgical management. Following drainage of the cyst the tremor disappeared, but recurred 18 months later. Repeat MRI showed that the thalamic cyst had refilled. As the initial tapping of the cyst had resulted in effective but only transient clinical improvement a cysto-peritoneal shunting procedure was performed. The clinical symptoms again disappeared and the child has now remained tremor free for 3 years.

Combination therapy with bosentan and sildenafil in idiopathic pulmonary arterial hypertension

It has been proposed that targeted treatments should be combined for patients with idiopathic pulmonary arterial hypertension (IPAH) responding insufficiently to monotherapy. This study followed the clinical course of nine patients with severe IPAH, in whom the endothelin receptor antagonist bosentan caused transient clinical improvement, eventually followed by a decline in exercise tolerance, who received adjunct treatment with the phospodiesterase-5-inhibitor sildenafil. Measurements included the 6-min walk distance (6MWD) and cardiopulmonary exercise testing (CPET). The 6MWD at baseline was 346+/-66 m and improved to 403+/-80 m 3 months after introduction of bosentan treatment. However, this effect was not sustained and, after an interval of 11+/-5 months, the walk distance had declined to 277+/-80 m. At this point, sildenafil was added to bosentan. Three months later, the 6MWD had increased to 392+/-61 m and the patients remained stable throughout the median follow-up of 9 months (range 6-12). Measurement of the maximum oxygen uptake during CPET confirmed these results. The combination of bosentan and sildenafil was well tolerated by all patients. These preliminary data suggest that combining bosentan and sildenafil may be safe and effective in patients with idiopathic pulmonary arterial hypertension.

Reversion of autoimmune lymphoproliferative syndrome with an antimalarial drug: preliminary results of a clinical cohort study and molecular observations.

Autoimmune lymphoproliferative syndrome (ALPS) is a paediatric disease characterized by lymphoproliferation and autoimmunity. Most patients are known to carry heterozygous mutations of the TNFRSF6 gene leading to diminished Fas-mediated apoptosis and failure of activated lymphocytes to undergo apoptosis. A subgroup of patients without the TNFRSF6 gene mutation has similar defective apoptosis and clinical features. No effective treatment has been reported so far. Glucocorticoids, intravenous immunoglobulin and/or immunosuppressive drugs have usually led to only transient clinical improvement. Seven ALPS patients (two type Ia and five type III) were treated with the antimalarial drug Fansidar. No toxicity was observed. An objective response was seen in six of them and, in two, the treatment was stopped without reappearance of the symptoms. Moreover, a marked decrease in interleukin-10 levels was observed in two patients during the treatment. We found that the drug induced apoptosis in activated lymphocytes through activation of the mitochondrial apoptotic pathway.

Differential DM20 mRNA expression distinguishes two distinct patterns of spontaneous recovery from murine autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is an animal model for multiple sclerosis (MS) mediated by T cells responding to CNS myelin proteins. Immunization of SWXJ mice with the immunodominant p139-151 peptide of myelin proteolipid protein (PLP) results in a relapsing-remitting pattern of EAE characterized by incomplete remyelination during clinical recovery. In the present study we observed two distinct clinical patterns of spontaneous remission during recovery from EAE, viz., sustained remission involving continuous neurologic improvement and aborted remission involving modest transient clinical improvement. We hypothesized that the ability to recover from autoimmune demyelination was directly linked to remyelination events that recapitulated developmental processes. Quantitative immunocytochemistry of CNS tissue showed decreased demyelination in mice undergoing sustained remission compared to mice undergoing aborted remission. Quantitative RT-PCR analysis showed elevated expression of DM20, the developmental isoform of PLP, in CNS tissue from mice undergoing sustained remission compared to mice undergoing aborted recovery. Moreover, DM20 expression was similarly elevated in CNS tissue from mice undergoing sustained recovery from EAE relapse. Our data indicate that expression of the developmental DM20 isoform of PLP is intimately associated with decreased demyelination and sustained clinical recovery from EAE. Thus, DM20 gene expression may provide an appropriate molecular target for promoting CNS remyelination and may serve as a useful marker for predicting clinical outcome and assessing the effectiveness of strategies aimed at promoting CNS tissue repair during autoimmune demyelinating disease.

Helium-oxygen mixtures in acute respiratory failure

Helium (He) has a much lower density than air. Thus, in turbulent flow conditions, helium-oxygen (He-O2) mixtures decrease resistance to flow compared to air-O2 mixtures. Theoretically, this effect could be beneficial in acute respiratory failure resulting from increased airway resistance, such as occurs in upper airway obstruction, asthma, and chronic obstructive pulmonary disease (COPD). Small uncontrolled series and case reports have indeed shown rapid albeit transient clinical improvement in upper airway disease. In asthma, studies have documented an increase in peak expiratory flow rate, an improvement in blood gases, and a reduction in pulsus paradoxus. In COPD, improved blood gases, expiratory flow, decreased dynamic hyperinflation, and reduced work of breathing and dyspnea have been observed. However, even though these encouraging results suggest that He-O2 should be included in the therapeutic options in such situations, there is no convincing data yet as to the exact place this gas mixture should occupy in treatment algorithms. This issue should clearly be explored further since He-O2 is a costly treatment not entirely devoid of potential deleterious effects mainly stemming from the ability of its low density to interfere with the proper functioning of mechanical ventilators.

CT-guided neurolysis. Status of the technique and current results

Both thoracic and lumbar sympathectomy and celiac ganglion block could be established as effective methods; side effects are rarely reported. Only the high accuracy of CT-guided positioning can make this possible. Severe side effects are merely sporadic if the proper technique is applied. We used 21G or 22G fine needles. All CT-guided percutaneous neurolysis methods require a proper blood coagulation. Most common CT scanners are suitable for neurolysis if there is enough room for maintaining sterile conditions. All neurolysis methods involve sterile puncture of the ganglia under local anesthesia, a test block with anesthetic and contrast agent to assess the clinical effect and the definitive block with a mixture of 96% ethanol and local anesthetic. This allows us to correct the position of the needle if we see improper distribution of the test block or unwanted side effects. Though inflammatory complications of the peritoneum due to puncture are rarely seen, we prefer the dorsal approach whenever possible. Seven of 20 legs showed at least transient clinical improvement after CT-guided lumbar sympathectomies; 13 legs had to be amputated. Results of the methods in the literature differ. For lumbar sympathectomy, improved perfusion is reported in 39-89%, depending on the pre-selection of the patient group. It was recently proved that sympathectomy not only improves perfusion of the skin but also of the muscle. The hypothesis of a steal effect after sympathectomy towards skin perfusion was disproved. Modern aggressive surgical and interventional treatment often leaves patients to sympathectomy whose reserves of collateralization are nearly exhausted. We presume this is the reason for the different results we found in our patient group. For thoracic sympathectomy the clinical treatment depends very much on the indications. Whereas palmar hyperhidrosis offers nearly 100% success, only 60-70% of patients with disturbance of perfusion have benefited. Results in celiac ganglia block also differ. Patients with carcinoma of the pancreas and other organs of the upper abdomen benefit in 80-100% of all cases, patients with chronic pancreatitis in 60-80%.

Endoscopic Intrasphincteric Injection of Botulinurn Toxin for the Treatment of Achalasia

Three patients with achalasia were treated with endoscopic injection of botulinum toxin (BoTx). BoTx (80 U) was injected via a sclerotherapy needle into the lower esophageal sphincter (LES). One patient complained of transient heartburn that resolved after omeprazole treatment. Two patients reported sustained symptomatic improvement. They were able to eat normally 48 h after treatment and have remained symptom free for 5 and 6.5 months, respectively. In these patients, esophageal manometry 4 months after treatment showed a marked reduction of resting LES pressure and the appearance of a previously absent LES relaxation after swallowing. The third patient had only a transient clinical improvement, with occasional dysphagia beginning 3 months after treatment. All patients showed unchanged aperistalsis of the esophageal body. Its less invasive nature compared with other therapeutic alternatives may give BoTX injection a role in the treatment of some patients with achalasia.