Paraneoplastic Association Research Articles

Stiff Person Syndrome and GAD Antibody-Spectrum Disorders.

Antibodies against glutamic acid decarboxylase (GAD), originally associated with stiff person syndrome (SPS), define the GAD antibody-spectrum disorders that also include cerebellar ataxia, autoimmune epilepsy, limbic encephalitis, progressive encephalomyelitis with rigidity and myoclonus (PERM), and eye movement disorders, all of which are characterized by autoimmune neuronal excitability. This article elaborates on the diagnostic criteria for SPS and SPS spectrum disorders, highlights disease mimics and misdiagnoses, describes the electrophysiologic mechanisms and underlying autoimmunity of stiffness and spasms, and provides a step-by-step therapeutic scheme. Very-high serum GAD antibody titers are diagnostic for GAD antibody-spectrum disorders and also predict the presence of GAD antibodies in the CSF, increased intrathecal synthesis, and reduced CSF γ-aminobutyric acid (GABA) levels. Low serum GAD antibody titers or the absence of antibodies generates diagnostic challenges that require careful distinction in patients with a variety of painful spasms and stiffness, including functional neurologic disorders. Antibodies against glycine receptors, first found in patients with PERM, are seen in 13% to 15% of patients with SPS, whereas amphiphysin and gephyrin antibodies, seen in 5% of patients with SPS spectrum disorders, predict a paraneoplastic association. GAD-IgG from different SPS spectrum disorders recognizes the same dominant GAD intracellular epitope and, although the pathogenicity is unclear, is an excellent diagnostic marker. The biological basis of muscle stiffness and spasms is related to autoimmune neuronal hyperexcitability caused by impaired reciprocal γ-aminobutyric acid-mediated (GABA-ergic) inhibition, which explains the therapeutic response to GABA-enhancing agents and immunotherapies. It is essential to distinguish SPS spectrum disorders from disease mimics to avoid both overdiagnoses and misdiagnoses, considering that SPS is treatable if managed correctly from the outset to prevent disease progression. A step-by-step, combination therapy of GABA-enhancing medications along with immunotherapies ensures prolonged clinical benefits.

PTH like substance secreting mesenchymal tumor causing oncogenic osteomalacia; unravelling the difficulties in localization – A report of 2 cases

BackgroundOncogenic osteomalacia is a rare paraneoplastic association of Phosphaturic mesenchymal tumor (PMT) secreting excessive levels of a PTH like substance. They usually remain undiagnosed and patients suffer for years. The rarity of this tumor and its non-specific clinical presentations poses great challenge to the treating surgeons. Its management is poorly described in literature. We report two of such rare cases without much diagnostic delay. Case reportWe had 2 cases; A 53-year-old south east Asian male with 6 months of debilitating pain over multiple sites, and another 44-year-old male patient with complaints of low back ache, and pain over both lower and upper limbs for 1.5 years. Both had low serum phosphorus and elevated FGF-23 values, but all other parameters were normal. A PMT was suspected and confirmed on a Ga68- DOTATOC scan in both cases, and on complete excision, their symptoms and the altered blood parameters got normalized. Histology was consistent with PMT. ConclusionAccurate and timely diagnosis of a PMT with non-specific features are extremely challenging, but not without solutions. Even though a tumor of rarity, with the appropriate imaging modalities like Ga68- DOTATOC scan, and estimation of FGF-23 and serum phosphorus levels, they can be diagnosed. Once identified, complete removal is often curative within a few months.

Increased prevalence of malignancies in patients with IgG4-related disease: implications for clinical care.

The association between cancer and IgG4-related disease (IgG4-RD) is evolving. The primary aim of this study was to investigate the prevalence of malignancies in IgG4-RD. The secondary aim was to describe the epidemiological and clinical characteristics of IgG4-RD patients with a history of cancer. Two hundred and ten patients with IgG4-RD were included in this retrospective study. IgG4-RD phenotypes, clinical and serological variables were analyzed. The prevalence of cancer in IgG4-RD was compared with that in the Italian population using the registry of the Global Cancer Observatory (GCO) of the World Health Organization. The Standardized Incidence Ratio (SIR) for cancer in IgG4-RD was obtained based on the 5-years Limited Duration Prevalence (2015-2020) of tumors in the Italian population. Thirty-seven/210 patients (18%) developed cancer before or after the diagnosis of IgG4-RD. Solid and hematologic tumors were more frequently observed in pancreato-biliary IgG4-RD. The SIR for malignancy in IgG4-RD patients was 2.54 higher than the general Italian population (p= 0.007). The SIR was 2.78 higher for males (p= 0.005) and 1.15 higher for females (p> 0.05). Thirty-two malignancies were diagnosed before and 16 after IgG4-RD diagnosis. Interval "from IgG4-RD to cancer" was shorter than that "from cancer to IgG4-RD". Most tumors occurring after IgG4-RD developed within 36 months from diagnosis of IgG4-RD. The prevalence of cancer in patients with IgG4-RD is increased compared with the Italian population and mechanistically suggests a possible paraneoplastic association. Close surveillance is warranted for the first 36 months after IgG4-RD diagnosis.

Immune Checkpoint Inhibitor-Associated Remitting Seronegative Symmetrical Synovitis With Pitting Edema: Description of a New Entity by CanRIO.

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is characterized by symmetrical synovitis with pitting edema and negative rheumatoid factor (RF). It has been described in a setting of malignancy, suggesting a paraneoplastic association. With the increasing use of immune checkpoint inhibitors (ICIs) for the treatment of cancers and emergence of immune-related adverse events (irAEs), our objective was to identify and describe cases of ICI-associated RS3PE (ICI-RS3PE) and compare them to non-ICI-RS3PE. The Canadian Research Group of Rheumatology in Immuno-Oncology (CanRIO) network is a collaboration of Canadian rheumatologists with experience in the management of patients with rheumatic irAEs (Rh-irAEs). Standardized data on adult patients with Rh-irAE have been collected as part of retrospective and prospective cohorts. In this study, detailed information on all cases of ICI-RS3PE from both cohorts were extracted and analyzed. We identified 11 cases of ICI-RS3PE. The most frequently observed malignancy was nonsmall cell lung cancer (4 of 11), followed by malignant melanoma (2 of 11) and cutaneous squamous cell carcinoma (2 of 11). The median time to onset of ICI-RS3PE was 26 weeks from ICI start and 52 weeks from diagnosis of malignancy. Seven patients had stable cancer prior to onset of ICI-RS3PE, 3 had partial response, and 1 had complete response. All patients received glucocorticoids. Conventional synthetic disease-modifying antirheumatic drugs (csDMARD) were needed in 10 patients. ICI-RS3PE may be an independent Rh-irAE, separate from paraneoplastic RS3PE. The symptoms of ICI-RS3PE responded well to glucocorticoids, but concomitant treatment with csDMARDs may be necessary.

Cardiac sarcoma presenting as paraneoplastic arthritis and clubbing: a case report and literature review

BackgroundCardiac tumours are rare, and clinical manifestations depend on the anatomical location. Symptoms can be the result of cardiac outflow anomalies, constitutional features such as fever, loss of weight, and/or paraneoplastic manifestations such as arthritis. To date, there has only been one other case report in the literature of cardiac sarcoma presenting as paraneoplastic arthropathy.Case presentationA 52-year-old woman presented with acute onset corticosteroid-resistant inflammatory polyarthralgia, clubbing and a systolic murmur. Transthoracic echocardiogram revealed a dilated left atrium with an echogenic mass and brain magnetic resonance imaging revealed multiple embolic infarcts. Histopathology following emergency resection showed a Grade 3 left atrial intimal sarcoma. The polyarthralgia and clubbing resolved soon after tumour removal. The patient went on to receive chemotherapy and remains in remission.ConclusionsThis case highlights the rare paraneoplastic association of cardiac sarcoma and arthropathy.

Collapsin response mediator protein 5-associated optic neuropathy: clinical characteristics, radiologic clues, and outcomes.

Collapsin response mediator protein 5-associated optic neuropathy (CRMP5-ON) is a rare entity of autoimmune optic neuropathy. This study aimed to review the neuro-ophthalmic findings and outcomes in a series of patients with CRMP5-ON to further characterize its clinical phenotype, radiologic clues, and outcomes. This was a retrospective case series and a single-center medical chart review of all patients with CRPM5-seropositive ON at the Department of Neurology, Beijing Tongren Hospital, from December 1, 2020, to March 31, 2023. The main outcome measures were neuro-ophthalmic manifestations, radiologic characteristics, and clinical outcomes of CRMP5-ON; coexisting neural autoantibody, paraneoplastic associations, and the impact of immunosuppressant therapy. Five patients were identified. Four (80%) were female, and the average age at onset was 59.4 years (range 53-69 years), with an average follow-up of 15.3 months (range 1.4-28.7 months). The average best-corrected visual acuity (BCVA) at nadir was 20/120 (range 20/20 to count fingers). Seven of ten affected eyes (70%) showed diffuse defects of the central field. Painless bilateral involvement and optic disk edema occurred in 100% of patients, combined with vitritis, uveitis, or retinitis in four (80%). Four patients (80%) had MRI abnormalities along the optic nerve (one patient with optic nerve enhancement and three patients had optic nerve sheath enhancement or peribulbar fat enhancement). Three patients (60%) had optic neuropathy with other neurologic symptoms. Four patients (80%) had confirmed cancer (two were small-cell lung carcinoma, one was papillary thyroid carcinoma and another was thymoma and invasive pulmonary adenocarcinoma). All cancers were identified after the presentation of the optic neuropathy. The intervention included IVIG, IVMP, surgery and chemotherapy. The average BCVA at the last follow-up was 20/50 (range 20/20 to count fingers). Three patients had surgery during the initial hospitalization, and were stable during the follow-up. Among two patients who received IVMP, both had improvement after treatment, although one patient had worsening non-ocular neurologic symptoms during the steroid taper. CRMP5-ON presented with optic disc edema, often bilateral involved and combined with vitreitis, retinitis, or uveitis. CRMP5-ON can present with MRI optic nerve or perineural optic nerve enhancement, especially in the optic nerve sheath. CRMP5-ON is closely related to paraneoplastic neurologic syndrome. Cancer screening and intervention are crucial to prognosis.

Autoimmune neuromyotonia.

Autoimmune neuromyotonia encompasses a group of rare immune-mediated neurological disorders frequently associated with anti-contactin-associated protein-like 2 (CASPR2) antibodies and featuring clinical and electrical signs of peripheral nerve hyperexcitability (PNH). We aim to summarize the current knowledge on immune-mediated neuromyotonia, focusing on clinical presentations, pathophysiology, and management. Neuromyotonia is a major feature of several autoimmune neurological syndromes characterized by PNH with or without central neurological system involvement. Experimental and clinical evidence suggest that anti-CASPR2 antibodies are directly pathogenic in autoimmune neuromyotonia patients. Neuromyotonia, a form of PNH, is a major feature in several syndromes associated with anti-CASPR2 antibodies, including cramp-fasciculation syndrome, Isaacs syndrome, Morvan syndrome, and autoimmune limbic encephalitis. Diagnosis relies on the identification of motor, sensory, and autonomic signs of PNH along with other neurological symptoms, anti-CASPR2 antibody-positivity, and of characteristic electroneuromyographic abnormalities. Paraneoplastic associations with thymoma are possible, especially in Morvan syndrome. Patients usually respond to immune-active treatments, including steroids, intravenous immunoglobulins, plasma exchanges, and rituximab.

Nephroblastoma cavoatrial tumor thrombus-A challenge to anesthesiologist.

Nephroblastoma cavoatrial tumor thrombus-A challenge to anesthesiologist.

Anti-NMDA-Receptor Encephalitis in a Patient with Ovarian Teratoma, Harboring Brain Histology of Varying Developmental Stages and Regions with Chronic Inflammation

Abstract Introduction/Objective Anti-NMDA-receptor encephalitis is a subacute, autoimmune disorder thought to be caused by autoantibodies directed against the N-methyl-D-aspartate (NMDA) receptor. Clinical symptoms of anti-NMDAR encephalitis may mimic schizophrenia and psychotic spectrum disorders or substance-induced psychosis. Although initially described in association with ovarian teratomas in women, anti-NMDAR encephalitis has been reported in individuals without paraneoplastic association, as well as in males. Herein, we report a case of a 29-year-old woman with suicidal ideation and other neuropsychiatric manifestations who was found to have a right ovarian cystic mass by imaging study. Microscopically, the resected ovarian mass is composed of mature skin, fat, cartilage and neural tissues. Nerve, ganglions and multiple brain tissues are present. Cerebellum including external granular cell layer (normally only seen in infants), cerebrum-like, choroid plexus and other neural elements are present. There is peripheral lymphoplasmacytic infiltrates around and within the neuroglial matrix. Cerebral spinal fluid was concurrently tested positive for Anti-NMDAR. The combined clinical, histological, and laboratory findings confirmed the above diagnosis. Although Anti-NMDAR encephalitis is a familiar entity to many clinical psychiatrist and neurologists, it is less commonly reported in the pathology literature. Its resultant relationship to cystic teratoma warrants awareness of this condition by pathologists. Methods/Case Report Case Report Results (if a Case Study enter NA) NA Conclusion Anti-NMDA-receptor encephalitis is related to cystic teratoma, therefore pathologists need to be aware of this condition.

N-Methyl-d-Aspartate Receptor Encephalitis Associated With COVID-19 Infection in a Toddler

Anti–N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis is characterized by mood and behavior changes, seizures, abnormal movements, autonomic instability, and encephalopathy. It occurs most commonly in young adults. A paraneoplastic association has been made with ovarian teratoma, although this is rare in children.1 More recently patients with anti-NMDAR encephalitis after viral infections have been reported, including herpes simplex virus (HSV), Japanese encephalitis virus, and now the 2019 novel coronavirus (SARS-CoV-2 or COVID-19).

Contactin-1 autoimmunity: Serologic, neurologic, and pathologic correlates.

ObjectiveTo determine serologic characteristics, frequency, phenotype, paraneoplastic associations, and electrodiagnostic and histopathologic features accompanying contactin-1 autoimmunity.MethodsArchived sera known to produce synaptic tissue-based immunofluorescence patterns were reevaluated, and contactin-1 specificity was confirmed by recombinant protein assays. Screening of 233 chronic/relapsing demyelinating neuropathies for additional cases was performed.ResultsWe identified 10 contactin-1 IgG seropositive cases. Frequency of contactin-1 immunoglobulin (Ig) G among tested Mayo Clinic chronic/relapsing demyelinating neuropathies was 2%. Sensory predominant presentations (n = 9, 90%), neuropathic pain (n = 6, 60%), and subacute progression (n = 5, 50%) were commonly encountered among contactin-1 neuropathies. Two patients had chronic immune sensory polyradiculopathy-like phenotype at presentation. Electrodiagnostic studies were consistent with demyelination (slowed conduction velocities and/or prolonged distal latencies) without conduction block. Markedly elevated CSF protein (median 222 mg/dL, range 69–960 mg/dL), thickening/gadolinium enhancement of nerve roots (4/5), and subperineural edema on nerve biopsy (4/4) were other characteristic features. Three cases were diagnosed with paraneoplastic demyelinating neuropathies (thymoma, n = 1; breast cancer, n = 1; plasmacytoma, n = 1). Four of the 9 patients treated with IV immunoglobulin demonstrated initial clinical improvement, but the favorable response was sustained in only 1 case (median follow-up, 60 months). Sustained clinical stabilization or improvement was observed among 3 of the 6 cases in whom second-line therapies (rituximab, cyclophosphamide, and azathioprine) were used.ConclusionContactin-1 IgG has a distinct sensory predominant presentation commonly associated with neuropathic pain, with demyelinating changes on electrophysiologic studies. A paraneoplastic cause should be considered. Testing of contactin-1 IgG among cases with similar presentations may guide immunotherapy selection, especially second-line immunotherapy consideration.

1716 Esophageal Squamous Cell Carcinoma-Associated Dancing Eye Syndrome in an Adult: Negative Paraneoplastic Antibodies Screen and Rapid Response to Intravenous Immunoglobulin and Methylprednisolone

INTRODUCTION: Dancing eye or opsoclonus-myoclonus syndrome is a rare paraneoplastic syndrome that has been mostly associated with small cell lung cancer. It was reported in association with esophageal cancer in one case. Here we report a second case. CASE DESCRIPTION/METHODS: A 59-year-old man presented with 5 weeks of rapidly worsening vertigo and gait difficulty that lead to frequent falls and inability to perform daily activities. About 5 weeks prior to presentation, he completed three rounds of cisplatin and 5-FU for recently diagnosed squamous cell carcinoma of the esophagus. He had long standing hypertension treated with hydrochlorothiazide, lisinopril, and carvedilol, and diabetes mellitus treated with glipizide, glyxambi, and sitagliptin. He denied alcohol, tobacco, or illicit drug use and recent viral infection. He was fully alert and oriented and afebrile. He had spontaneous, involuntary, arrhythmic, conjugate, multidirectional saccades occurring in all directions of gaze without a saccadic interval and pronounced ataxia on standing associated with unsteadiness. Complete blood count and routine chemistry were unremarkable. Brain MRI with and without contrast revealed no evidence of intracranial hemorrhage, mass lesion, acute infarct or pathologic enhancement. HIV screen was negative. Hepatits C virus antibody was non-reactive. Paraneoplastic autoantibodies screening was negative. He received 5 day course of 0.4g/kg/day intravenous immunoglobulin (IVIG) and 250 mg BID methylprednisolone with marked improvement of rhythmic eye beating at rest, coordination of multidirectional eye movements, ataxia, and vertigo by day 3. He was discharged to acute rehabilitation facility on day 8. DISCUSSION: Our patient has dancing eye or opsoclonus-myoclonus syndrome that followed the diagnosis of esophageal cancer and rapidly responded to IVIG and methylprednisolone, strongly suggesting a paraneoplastic association. Interestingly and consistent with the single case previously reported of this association, paraneoplastic autoantibodies screen was negative.

Collapsin Response-Mediator Protein 5–Associated Retinitis, Vitritis, and Optic Disc Edema

Collapsin response-mediator protein 5 (CRMP5) immunoglobulin G (IgG) has been associated with paraneoplastic optic neuritis, vitritis, retinitis, or a combination thereof, but few reports of these findings exist in the literature. We reviewed the neuro-ophthalmic findings and visual outcomes in a large series of CRMP5 IgG-positive patients to characterize further its clinical phenotype and response to treatment. Retrospective case series. Seventy-six patients with CRMP5 autoimmunity examined at the Mayo Clinic, Rochester, Minnesota. Single academic medical center chart review of all CRMP5 IgG-positive (serum titer, >1:240) patients seen between 2001 and2017. Neuro-ophthalmic manifestations and outcomes of CRMP5 autoimmunity, coexisting neural autoantibody presence and paraneoplastic associations, and the impact of immunosuppressant therapy. Twenty-nine of 76 patients (38%) demonstrated neuro-ophthalmic manifestations. Of the 29 patients with neuro-ophthalmic findings, the median age was 67 years (range, 33-88 years) and 20 (69%) were women. Cancer was diagnosed in 62% of the patients (small-cell carcinoma in 83%). Neuro-ophthalmic symptoms occurred before the diagnosis of cancer in 72%. Seventeen of 29 patients (59%) showed ocular (i.e., anterior visual pathway or intraocular) manifestations; presenting median visual acuity was 20/50 (range, 20/20-counting fingers) and the final median visual acuity was 20/40 (range, 20/20-hand movements). Fourteen of 17 patients (82%) demonstrated optic neuropathy, with 12 of these patients also showing retinitis or uveitis. Three of 17 patients (18%) showed retinitis or uveitis without optic neuropathy. All 12 patients with optic neuropathy and a documented fundus examination at visual symptom onset demonstrated optic disc edema. No patients showed optic nerve enhancement on magnetic resonance imaging. Twelve of 29 patients (41%) demonstrated ocular motility dysfunction consisting of central nystagmus and diplopia. Among those receiving immunosuppressive therapy, visual function improved in 50%. In our cohort of 29 CRMP5 IgG-positive patients with neuro-ophthalmic manifestations, optic neuropathy presented with optic disc edema, often associated with uveitis, retinitis, or both. The combination of retinitis, vitritis, and optic disc edema without optic nerve enhancement should prompt serologic testing for CRMP5 IgG to expedite vision-sparing immunosuppressant therapy and a targeted search for a systemic cancer.

Anti-NMDA receptor encephalitis: a case study and illness overview.

Anti-N-methyl D-aspartate (NMDA) receptor (anti-NMDAR) encephalitis is among one of the most common autoimmune encephalitides. However, variations in clinical presentation and nonsequential multiphasic course often lead to delays in diagnosis. The mild encephalitis (ME) hypothesis suggests a pathogenetic mechanism of low-level neuroinflammation sharing symptom overlap between anti-NMDAR encephalitis and other psychiatric disorders including schizophrenia. Clinical symptoms of anti-NMDAR encephalitis may mimic schizophrenia and psychotic spectrum disorders or substance-induced psychosis. Although initially described in association with ovarian teratomas in women, anti-NMDAR encephalitis has been reported in individuals without paraneoplastic association, as well as in males. It can affect all age groups but is usually lower in prevalence in individuals greater than 50 years old, and it affects females more than males. Clinical evaluation is supported by laboratory workup, which includes cerebrospinal fluid (CSF) assays. The latter often reveals lymphocytic pleocytosis or oligoclonal bands with normal to elevated CSF protein. CSF testing for anti-NMDAR antibodies facilitates diagnostic confirmation. Serum anti-NMDAR antibody assays are not as sensitive as CSF assays. Management includes symptomatic treatment and immunotherapy.

Optic neuritis as the initial clinical presentation of limbic encephalitis: a case report

BackgroundLimbic encephalitis is characterized by rapid onset of working memory deficit, mood changes, and often seizures. The condition has a strong paraneoplastic association, but not all cases are invariably due to tumors.Case presentationWe present a case of limbic encephalitis in a Chinese patient who initially presented to our hospital with optic neuritis and no other neurological symptoms. The diagnosis was made radiologically, and cognitive and neurological symptoms did not occur until 5 months later. Extensive investigations for autoimmune, infective, and neoplastic causes were all negative. A working diagnosis of paraneoplastic neurological syndrome was made, and the patient is being managed with high-dose steroid therapy according to the Optic Neuritis Treatment Trial protocol during relapses, as well as with tumor surveillance.ConclusionsThis case highlights ocular symptoms as important clues for diagnosing neurological diseases, as well as autoimmune encephalitis as an important differential diagnosis in the management of “idiopathic” optic neuritis in the Chinese population.

Investigation of myositis and scleroderma specific autoantibodies in patients with lung cancer

BackgroundThe close temporal association between onset of some connective tissue diseases and cancer suggests a paraneoplastic association. Adult patients with scleroderma with anti-RNA polymerase III autoantibodies and adult patients with dermatomyositis with anti-transcriptional intermediary factor 1 (anti-TIF1) or anti-nuclear matrix protein 2 (anti-NXP2) autoantibodies have a significantly increased risk of developing cancer. Autoantibodies may serve as biomarkers for early detection of cancer and also could be relevant for prediction of responses to immune therapies. We aimed to test whether myositis and scleroderma specific or associated autoantibodies are detectable in individuals with lung cancer.MethodsSerum from 60 Caucasian patients with lung cancer (30 with small cell lung cancer, 30 with non-small cell lung cancer) was screened for myositis and scleroderma specific and associated autoantibodies by radiolabelled immunoprecipitation.ResultsAnti-TIF1, anti-NXP2 or anti-RNA polymerase III autoantibodies were not detected in any of the 60 patients with lung cancer. Anti-glycyl-transfer RNA (tRNA) synthetase (anti-EJ) autoantibodies were detected in one patient with non-small cell lung cancer. No other known myositis or scleroderma autoantibodies were identified.ConclusionsMyositis and scleroderma specific autoantibodies, including anti-TIF1, anti-NXP2 and anti-RNA polymerase III, are rare in patients with lung cancer without an autoimmune disease. We report here the first case of anti-EJ autoantibodies being detected in a patient with lung cancer without clinical or radiographic evidence of the anti-synthetase syndrome.

Autoimmune Epilepsy: The Evolving Science of Neural Autoimmunity and Its Impact on Epilepsy Management.

Autoimmune epilepsy is increasingly recognized as a distinct clinical entity, driven in large part by the recent discovery of neural autoantibodies in patients with isolated or predominant epilepsy presentations. Detection of neural autoantibodies in high-risk epilepsy patients supports an immune-mediated cause of seizures and, if applicable, directs the search for an underlying cancer when the paraneoplastic association of the associated antibody is compelling. Early diagnosis of autoimmune epilepsy is crucial, as prompt initiation of immunosuppressive treatment increases the likelihood of achieving either seizure freedom or a substantial reduction in seizure frequency. A practical clinical approach that incorporates risk scores to guide patient selection on the basis of clinical features, neural autoantibodies, and a treatment trial of immunotherapy is suggested. Elucidating an immunological basis of epilepsy provides neurologists with wider treatment options (incorporating immune-suppressive treatment), in addition to standard antiepileptic drugs, which often improves patient outcomes.

Liver Involvement in Hodgkin's Lymphoma: Types of Injuries and Therapeutic Implications

The hepatocytolysis raises questions on following therapeutic conduct when it occurs during chemotherapy for Hodgkin's lymphoma, expression of its liver toxicity. But the onset of primary liver Hodgkin's lymphoma, including the form manifested by acute liver failure, poses even greater problems, as in the case of occurrence of vanishing bile duct syndrome - expression of a paraneoplastic syndrome, hemophagocytic lymphohistiocytosis, peliosis hepatis or association of lymphoma with infection with hepatitis viruses or human immunodeficiency virus or different autoimmune diseases. This review summarizes the clinical experience acquired on the relationship between Hodgkin's lymphoma and liver, from the point of view of clinical manifestations, used treatments and clinical evolution. Suggestions on the course of treatment in patients with Hodgkin's lymphoma and liver damage have been formulated starting from the metabolism and elimination of chemotherapy drugs and taking into account the clinical experience of published clinical trials and cases. This review is a synthesis of knowledge obtained in this field, during the time, of therapeutic possibilities and limits, and formulates potential future milestones for research.

Specific autoantibodies in dermatomyositis: a helpful tool to classify different clinical subsets.

Autoantibodies are important in the diagnosis of dermatomyositis. They can be divided in two different groups: myositis-associated autoantibodies (MAA) prevailing in overlap syndromes, and myositis-specific autoantibodies (MSA), with diagnostic specificity exceeding 90%. Our purpose was to detect retrospectively the prevalence of the most common MSAs in a group of 19 adult DM patients (13 women, 6 men). A severe DM (SDM), with extensive cutaneous and muscular manifestations, dysphagia, and sometimes pneumopathy, was detected in ten cases. Three patients had a mild DM (MDM), with little muscle and skin impairment, and a short course. Four patients suffered from amyopathic DM (ADM), two from paraneoplastic DM (PDM). Each serum was tested for ANA, ENA, MAAs, MSAs. Myositis-specific autoantibodies were detected in 15 cases. The most frequent was anti-TIF1γ, associated with SDM or PDM in four out of seven cases. Anti-MDA5 antibodies were recorded in a SDM and in a ADM with lung fibrosis. Anti-Mi2 and anti-SRP antibodies were both detected in a MDM and in a SDM, whereas anti-SAE1 in a amyopathic form. Other antibodies (anti-NXP2, -Jo1, -PL7, -PL12, -OJ) were found in single patients with SDM. Our series confirmed that specific autoantibodies could be helpful to classify different clinical subsets, particularly in the case of paraneoplastic forms or association with pneumopathy. Moreover, they can help in predicting the disease evolution and influence therapeutic strategies. A greater number of cases should be useful to highlight the clinical and pathogenic role of these antibodies, and develop a homogeneous protocol for diagnosis and treatment.

Wilms tumour with intracardiac extension - multimodal approach to a challenging case.

Sir, Anaesthesia for surgery for Wilm's tumour in advanced stage is a great challenge as the condition is often seen in young children with limited reserve further complicated by disease process, prior chemotherapy and paraneoplastic associations such as hypertension and coagulopathy.[1] A 2-year-old child was admitted to our institution with a biopsy proven right nephroblastoma that did not respond to neoadjuvant chemotherapy. Computerised tomography scan revealed a large right renal tumour with a cavoatrial thrombus [Figure 1]. Echocardiogram revealed a large tumour thrombus (20 mm × 15 mm) in the right atrium encroaching the tricuspid valve and mild pericardial effusion. The treatment plan was right radical nephrectomy with inferior vena caval (IVC) thrombectomy and right atriotomy under cardiopulmonary bypass. Figure 1 Pre-operative computerised tomography urogram demonstrates large right renal tumour with extension of tumour thrombus into right atrium Pre-anaesthetic evaluation revealed an emaciated child weighing 13 kg with a disproportionately protuberant abdomen, pallor, pedal oedema and tachycardia. Her coagulation profile and renal function tests were normal. The day before surgery, right renal artery angioembolisation was undertaken to decrease tumour vascularity and ease surgical extirpation. Anaesthesia was induced with fentanyl 2 μg/kg, ketamine 2 mg/kg and vecuronium 0.08 mg/kg. Monitoring included electrocardiogram, pulse oximetry, end-tidal carbon dioxide, central venous pressure, intra-arterial blood pressure, temperature and urine output. Mechanical ventilation with a tidal volume of 6 ml/kg was instituted with airway pressure maintained around 28 mmHg and the end-tidal carbon dioxide maintained at around 42 mmHg. Anticipating haemodynamic fluctuations, two arterial lines and one central venous catheter were secured after induction. Through a right thoraco-abdominal incision, right radical nephrectomy, cavotomy and extraction of vena caval thrombus was performed [Figure 2]. Blood loss encountered was about 100 ml. Moderate degree of hypotension was experienced which responded to volume replacement. Intraoperative echocardiography demonstrated the persistence of right atrial thrombus. Right atriotomy was then undertaken under deep hypothermic circulatory arrest (DHCA) with a core body temperature of 18°C and the thrombus was extracted. The total circulatory arrest time was 3 min. After clearance of tumour, circulation was restored, and atrial reconstruction was completed during the rewarming phase. The patient required inotropic support (adrenaline 0.03 μg/kg/min) during the procedure. Approximately 300 ml of packed red blood cells and 350 ml of fresh frozen plasma were transfused. The total duration of the procedure was 8 h. The child was electively ventilated and extubated on the following day. By the 5th day, she was moved out of the Intensive Care Unit and discharged on the 14th day. Post-operative period was fairly uneventful except for mild renal dysfunction which responded to conservative management. Figure 2 Intraoperative appearance of tumour Wilm's tumour is the fourth most common paediatric malignancy.[2] Complete surgical clearance improves the prognosis but may be demanding in advanced lesions as it has the propensity to extend into the cardiac chambers along the inferior vena cava. A multidisciplinary approach will facilitate favourable outcome in such situations.[3] Intraoperative course may be stormy and the anaesthesiologist should be equipped to tackle this. The major intraoperative concerns are heat loss, fluid balance, inadequate ventilation due to raised intra-abdominal pressure, haemodynamic fluctuations in the face of intermittent IVC compression, tumour embolisation and major haemorrhage. Cardiopulmonary bypass is employed to avoid tumour embolisation.[4] DHCA enabled excellent surgical exposure, but the duration of circulatory arrest had to be limited to ward off complications.[5] The disproportionate size of the tumour in comparison to the weight of the child and its physiological consequences made this case unique. A multidisciplinary approach and close coordination between various specialties is what saw the child through the technically demanding procedure and convalescence. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.