anti-Hu Antibodies Research Articles

Chronic Gastrointestinal Pseudoobstruction with Histological Hypoganglionosis and Non-Paraneoplastic Anti-Hu Antibody Positivity: A Case Report

Chronic Gastrointestinal Pseudoobstruction with Histological Hypoganglionosis and Non-Paraneoplastic Anti-Hu Antibody Positivity: A Case Report

Paraneoplastic neurological syndromes associated with anti-Hu antibodies in an ovarian cancer patient: a case report and narrative literature review

Paraneoplastic neurological syndromes associated with anti-Hu antibodies in an ovarian cancer patient: a case report and narrative literature review

Comprehensive Evaluation of Sporadic Late-Onset Cerebellar Ataxias: Clinical Presentation, Diagnostic Challenges, and Treatment Outcomes.

Sporadic late-onset cerebellar ataxias (SLOCA) present a diagnostic challenge due to their heterogeneous etiologies and complex clinical manifestations. This retrospective study aimed to conduct a comprehensive evaluation of six male patients diagnosed with SLOCA, with a mean age of 55 years and an average symptom onset at 47 years. All patients presented with gait and balance disturbances, with additional sensory abnormalities observed in two cases. Neurological examinations revealed varied cerebellar syndromes, including static and static-kinetic presentations, accompanied by peripheral neurogenic syndromes in some instances. Brain MRI findings showed cerebellar atrophy, predominantly involving the vermis, in a subset of patients. Biochemical and serological investigations yielded mostly unremarkable results, although two patients exhibited significant vitamin E deficiency and anti-Hu antibodies (anti-neuronal nuclear antibody type 1). Electromyography confirmed sensory axonal neuropathy in those with peripheral neurogenic syndromes. Treatment with TOCO 500 mg (Vitamin E) was administered to four patients, with follow-up indicating stable disease progression in two cases. This study underscores the complexity of SLOCA and the need for a multidisciplinary approach to diagnosis and management. Further research is warranted to elucidate the underlying mechanisms and improve clinical outcomes for affected individuals.

Anti-Hu antibody associated paraneoplastic neurological syndrome in a child with ganglioneuroblastoma: A rare case report and literature review.

Paraneoplastic neurological syndrome with anti-Hu antibody (Hu-PNS) is a neurological disorder that occur in patients with malignancy. The syndrome has a wide range of presentations and can present before diagnosis of primary malignancy. Familiarity with these paraneoplastic neurological syndromes can help early recognition and take appropriate regimens. Diagnosis and treatment of Hu-PNS. This is retrospective study that analyzed the clinical data of this case. Through retrospective analysis and targeted antibody screening, serum anti-Hu antibody was detected. Subsequent spinal imaging revealed a mass in the paraspinal region, which was confirmed as ganglioneuroblastoma by pathologic examination. The child was treated with a course of intravenous immunoglobulin and radical surgical operation without chemotherapy. The neurological symptoms were gradually improved and no signs indicate disease progression or tumor recurrence. Hu-PNS has rarely been reported in children with ganglioneuroblastomas. They can mimic non-neoplastic processes, making detection and diagnosis difficult. Serum and/or cerebrospinal fluid onconeural antibody can strongly indicate occult cancers. Early detection of paraneoplastic neurological syndromes can help take appropriate regimens and improve prognosis.

Dysautonomia in anti-Hu paraneoplastic neurological syndromes.

Dysautonomia has been associated with paraneoplastic neurological syndrome (PNS)-related mortality in anti-Hu PNS, but its frequency and spectrum remain ill-defined. We describe anti-Hu patients with dysautonomia, estimate its frequency, and compare them to patients without dysautonomia. Patients with anti-Hu antibodies diagnosed in the study centre (1990-2022) were retrospectively reviewed; those with autonomic signs and symptoms were identified. Among 477 anti-Hu patients, 126 (26%) had dysautonomia (the only PNS manifestation in 7/126, 6%); gastrointestinal (82/126, 65%), cardiovascular (64/126, 51%), urogenital (24/126, 19%), pupillomotor/secretomotor (each, 11/126, 9%), and central hypoventilation (10/126, 8%). Patients with isolated CNS involvement less frequently had gastrointestinal dysautonomia than those with peripheral (alone or combined with CNS) involvement (7/23, 30% vs. 31/44, 70% vs. 37/52, 71%; P = 0.002); while more frequently central hypoventilation (7/23, 30% vs. 1/44, 2.3% vs. 2/52, 4%; P < 0.001) and/or cardiovascular alterations (18/23, 78% vs. 20/44, 45% vs. 26/52, 50%; P = 0.055). Median [95% CI] overall survival was not significantly different between patients with (37 [17; 91] months) or without dysautonomia (28 [22; 39] months; P = 0.78). Cardiovascular dysautonomia (HR: 1.57, 95% CI [1.05; 2.36]; P = 0.030) and central hypoventilation (HR: 3.51, 95% CI [1.54; 8.01]; P = 0.003) were associated with a higher risk of death, and secretomotor dysautonomia a lower risk (HR: 0.28, 95% CI [0.09; 0.89]; P = 0.032). Patients with cardiovascular dysautonomia dying ≤ 1year from clinical onset had severe CNS (21/27, 78%), frequently brainstem (13/27, 48%), involvement. Anti-Hu PNS dysautonomia is rarely isolated, frequently gastrointestinal, cardiovascular and urogenital. CNS dysfunction, particularly brainstem, associates with lethal cardiovascular alterations and central hypoventilation, while peripheral involvement preferentially associates with gastrointestinal or secretomotor dysautonomia, being the latest more indolent.

Paraneoplastic Neurological Syndromes as Initial Presentation of Tumors: An Eight-Year Single-Center Experience

Background: Paraneoplastic Neurological Syndromes (PNS) comprise a diverse group of disorders propagated by immune-mediated effects of malignant tumors on neural tissue. Methods: A single-center longitudinal study was performed including consecutive adult patients treated at a tertiary academic hospital between 2015 and 2023 and diagnosed with PNS. PNS were ascertained using the 2004 and the revised 2021 PNS-Care diagnostic criteria. Results: Thirteen patients who fulfilled the 2004 definite PNS criteria were included. PNS comprise diverse neurological syndromes, with neuromuscular junction disorders (54%) and limbic encephalitis (31%) being predominant. PNS-related antibodies were detected in 85% of cases, including anti-AChR (n = 4), anti-P/Q-VGCC (n = 3), anti-Hu (n = 3), anti-Yo (n = 1), anti-Ma (n = 1), anti-titin (n = 1), anti-IgLON5 (n = 1), and anti-GAD65 (n = 1). Thymoma (31%), small-cell lung cancer (23%), and papillary thyroid carcinoma (18%) were the most frequent tumors. Imaging abnormalities were evident in 33% of cases. Early immunotherapy within 4-weeks from symptom onset was associated with favorable outcomes. At a mean follow-up of 2 ± 1 years, two patients with anti-Hu and anti-Yo antibodies died (18%). Four and three patients fulfilled the 2021 PNS-Care diagnostic criteria for definite and probable PNS, respectively. Conclusions: This study highlights the clinical heterogeneity of PNS, emphasizing the need for early suspicion and prompt treatment initiation for optimal outcomes.

Autoimmune encephalitis associated with anti-N-methyl-D-aspartate receptor and anti-HU antibodies successfully treated with carboplatin and etoposide for small-cell lung cancer: A case report

Autoimmune encephalitis associated with anti-N-methyl-D-aspartate receptor and anti-HU antibodies successfully treated with carboplatin and etoposide for small-cell lung cancer: A case report

Anti-Hu antibody seropositive neuropathy with large and small fiber involvement mimicking alcoholic neuropathy: a case report

BackgroundAnti-Hu antibody neuropathy is considered a rare acquired peripheral neuropathy, but common among paraneoplastic syndromes. Typically, is described as subacute sensory neuronopathy and electrophysiological findings are usually suggestive of a sensory axonal neuropathy.Case presentationWe report the case of a 67-year-old man referred to our clinic with a 4-month history of progressive pain and paresthesias of distal lower limbs. He had a 30-year history of alcohol abuse and smoking. Alcoholic neuropathy was considered the most likely diagnosis, considering his history and evaluation. The patient’s neurological examination revealed symmetric bilateral superficial and deep sensory loss in the lower extremities, reduced Achilles tendon reflexes and wide based gait. Electrophysiological testing was suggestive of axonal sensory-motor polyneuropathy and small fiber involvement. Even though alcohol consumption was discontinued, symptoms gradually worsened. Further testing was performed and the patient was found seropositive for anti-Hu antibody. Small-cell lung cancer was detected later, but patient passed away before treatment for cancer was administrated.ConclusionsThe aim of our paper is to report a case of a rare paraneoplastic syndrome that can cause progressive sensory-motor neuropathy with large and small fiber involvement, which should be rapidly differentially diagnosed from other neuropathies, so that the underlying cause can be identified and, potentially, treated.

OA17 Rheumatoid meningitis - a rare complication of rheumatoid arthritis

Abstract Introduction A wide spectrum of neurological complications can occur in rheumatoid arthritis (RA) including peripheral neuropathy, mononeuritis multiplex and rheumatoid vasculitis. Cerebrovascular disease is also common. We describe a rare neurological complication of RA. Case description The patient was first diagnosed with seropositive RA in 2015 at the age of 68. His rheumatoid factor at presentation was 144 kIU/L and CCP antibodies &amp;gt;340 U/mL. His background include alcohol excess and obstructive sleep apnoea with peripheral neuropathy attributed to alcohol. Nerve conduction studies demonstrated axonal neuropathy. By 2016, he had achieved good disease control with combination methotrexate and sulfasalazine. In 2018, he was admitted to stroke services with right arm weakness and focal neurological deficit on examination. An urgent CT head showed possible right parietal extra dural haemmorhage. His CRP was &amp;lt;5, ESR 24 with a normal ANA. Borrelia, syphilis and HIV screening were normal. Anti-glutamic acid decarboxylase (GAD), anti-amphiphysin, anti-Hu, anti-Yo and anti-Ri antibodies were all negative. Lumbar puncture revealed a normal glucose and red blood cells count but the CSF protein was raised at 851 mg/L with a lymphocyte count of 9/ul. Gram stain, culture, viral PCR for HSV, VZV, enterovirus, parechovirus and adenovirus were normal and CSF cytology demonstrated a lymphocyte pleocytosis. Subsequent contrast MRI head scan showed leptomeningeal enhancement with gadolinium contrast. MRI of the cervical spine and brachial plexus was normal and an EMG/NCS of the upper limb demonstrated an incidental ulnar nerve compression at the elbow. Following neurology input, the leptomeningeal enhancement was thought to represent rheumatoid meningitis (RM). He was treated with 1 mg/kg prednisolone and rituximab with prompt and complete recovery. He remains well from both the perspective of his RA and RM. Discussion RM is a rare form of aseptic meningitis. Aseptic meningitis is commonly defined as clinical and CSF evidence of meningeal inflammation in the absence of an infectious aetiology. The vast differential includes malignancies, drug-induced and autoimmune diseases, for example lupus and sarcoidosis. The diagnosis of RM requires a high index of suspicion as well as exclusion of other causes. Historically RM was diagnosed at post-mortem but MRI scanning means pre-mortem diagnosis is possible. It is considered rare but serious manifestation of RA. Case reports suggest RM usually occurs in those with long standing seropositive RA but RM has been described in the early stages of RA and even as a presenting feature. Peripheral disease activity does not correlate with occurrence of RM. The clinical presentations vary depending on the brain structure involved and can include motor or sensory deficits, cognitive disturbance and seizures. It may mimic many other conditions. Radiological findings will not distinguish RM from other causes of aseptic meningitis. CSF finding of lymphocytosis and rheumatoid factor (if available) may help distinguish RM from other causes. Meningeal biopsy can confirm the diagnosis. Due to the rarity of RM, there are no current guidelines on treatment. Historically, corticosteroids are the main induction agent. There are case reports highlighting possible success from the addition of cyclophosphamide and rituximab. Case series also highlight a significant mortality rate in excess of 60% even despite treatment. This may represent publication and historical bias. Key learning points Rheumatoid meningitis (RM) is a rare but serious complication of rheumatoid arthritis. RM may not correlate with disease activity nor disease duration. Diagnosis is a challenge due to its wide clinical phenotype as well as the non-specificity of imaging, lumbar puncture and serological findings. Treatment options are based on case reports and series and include corticosteroids, rituximab and cyclophosphamide.

Paraneoplastic Neurologic Syndrome in Small Cell Lung Carcinoma

A 54-year-old male smoker, previously in good health, was admitted to the hospital due to a tingling sensation in his upper and lower extremities. He reported difficulty walking due to a loss of balance and numbness, leading to an initial diagnosis of chronic inflammatory demyelinating polyneuropathy. Brain and spine magnetic resonance imaging, along with needle electromyography, yielded inconclusive findings. However, a nerve conduction study indicated a length-dependent pattern of sensory-dominant polyneuropathy. A cerebrospinal fluid study did not reveal any specific findings in terms of cell numbers, proteins, or immune tests. Following hospitalization, the patient reported progressive dizziness upon standing, leading to a preliminary diagnosis of orthostatic hypotension. However, a positive anti-Hu autoantibody test, along with chest computed tomography and positron emission tomography scans, revealed a mass in the left interlobar lymph node, suggestive of lung cancer. An endoscopic biopsy confirmed the presence of small cell lung cancer (SCLC). The patient underwent chemo-radiation treatment for the SCLC and immunoglobulin therapy for sensory ganglionopathy. As a result, a definitive diagnosis of paraneoplastic neurologic syndrome was made. Although such cases are rare, our observations suggest that symptoms of dysautonomia and sensory ganglionopathy may be associated with the production of anti-Hu antibodies.

Inaugural dropped head syndrome and camptocormia in inflammatory myopathies: a retrospective study.

Inaugural axial muscle involvement, defined as dropped head syndrome (DHS) and/or camptocormia (CC), is poorly described in inflammatory myopathies (IM). This study aimed to further characterize IM patients with inaugural DHS/CC, their outcome and care management. This retrospective study included IM patients diagnosed between 2000 and 2021. The main inclusion criterion was IM revealed by axial muscle deficit (DHS/CC). Twenty-seven patients were included; median (IQR) age at first symptoms was 66.0 years (55.5-75.0); 21 were female (77.8%). There were nine IBM, 33.3%, nine overlap myositis (OM, 33.3%), five DM, 18.5%, two immune checkpoint inhibitor-related myositis (7.4%), one focal myositis (3.7%) and one myositis with anti-Hu antibodies (3.7%). Age at first symptoms was ≤70 years in 16 patients (59.3%), including all DM patients and 8/9 OM patients (88.9%). In this group, partial remission of the disease was obtained in 9/16 (56.3%) and complete remission in 1/16 patients (6.3%); regression of DHS/CC was achieved in 3/16 patients (18.8%). Conversely, in the group of 11 patients aged >70 years at first symptoms, there were eight IBM (72.7%). Partial remission was obtained in 5/11 patients (45.5%), the disease was stable in 6/11 patients (54.5%); no complete remission was obtained nor regression of DHS/CC. The analysis of IM patients with inaugural DHS/CC delineates two groups of patients according to the age at first symptoms in terms of clinical and outcome specificities, and proposes an adapted diagnostic and care management approach to prevent long-term complications.

Anti-SOX1 Antibody-positive Small-cell Lung Cancer That Triggered Opsoclonus.

A 72-year-old woman with opsoclonus visited our hospital and was diagnosed with small-cell lung cancer. Blood tests revealed anti-SOX1 antibodies, so the patient was diagnosed with paraneoplastic opsoclonus-myoclonus syndrome. After steroid pulse therapy was started, chemotherapy of treatment, the opsoclonus showed an improving trend. Anti-Ri and anti-Hu antibodies have been reported as autoantibodies associated with neoplastic opsoclonus-myoclonus syndrome; however, there are no such reports concerning anti-SOX1 antibody. Therefore, this is a valuable case.

Early and Aggressive Treatment May Modify Anti-Hu Associated Encephalitis Prognosis.

Anti-Hu encephalitis is a paraneoplastic syndrome in adults. In children, rare cases of anti-Hu encephalitis were reported mostly without underlying tumors and clinical outcome are usually severe. Here, we describe a 4-year-old girl who developed cerebellar syndrome with abnormal behavior. The brain magnetic resonance imaging showed several T2/fluid-attenuated inversion recovery bilateral brain lesions and autoimmune assessment showed positive anti-Hu antibodies. Computed tomography scan revealed ganglioneuroblastoma which was surgically removed 3 months after onset. Aggressive immunotherapy including dexamethasone, rituximab, and intravenous immunoglobulins were used and a marked neurological improvement soon after 9 months of onset was observed with the child being able to go back to school. The short delay between diagnosis and start of aggressive immunotherapy demonstrate the paramount importance of early diagnosis and early specific therapy after onset of symptoms.

Spontaneous Regression of Lung Carcinoma: An Essential Review

Lung cancer is the second leading cause of cancer in both males and females in the United States, as it has been estimated that 200,000 new cases will appear in males and females in the U.S, accounting for 14% of new cancers. Lung cancer accounts for 25% of cancer fatalities and has the lowest survival rates. Cancer Spontaneous Regression (SR) is defined as either partial or complete, and temporary or permanent, disappearance without appropriate treatment for the disease, and is a very rare phenomenon of unknown mechanism. The exact incidence of cancer SR is unknown. 176 cases of cancer SR have been reported from 1900 to 1964 with an assessed incidence of 1/ 60,000-100,000 cancer patients, whereas another research found total 15 cases from 1954 to 1997, and more recently 741 cases of SR of malignant diseases in the literature between 1900 and 1987 have been recorded. SR cases concerned several types of malignancies such as lymphoma, leukemia, retinoblastoma, neuroblastoma, melanoma, choriocarcinoma, renal, bladder, and breast cancer, and represented 69% of all SR cases, whereas lung cancer SR only observed in 2.6% of all patients with SR. A few cases reported that SR is an extremely rare biological event in primary lung cancer, and in particular, SR of non-small cell lung cancer (NSCLC) has been scarcely reported. The SR incidence of advanced NSCLC is relatively low, as approximately 20 cases were recorded from 1950 to 2004, and no more than 15 new cases have been reported in the last 12 years. 10 articles describing NSCLC SR between 1997and 2018 have also been observed. Currently, 17 well-documented case reports of lung cancer SR concerning NSCLC and small cell lung cancer (SCLC) have been described. A total of 25 cases of lung cancer were identified between 1987and 2020. Squamous cell carcinoma (SQCLC) accounted for 10 cases, followed by NSCLC not otherwise defined and adenocarcinomas. The pathogenesis of SR cancer is poorly understood, however recent investigations revealed the role of immunological mechanisms, consequently indicating possible therapy options by specific immunotherapy in the future. It has also been supposed that there may be an immunological association between the stimulus of the biopsies and the SR. Recent researches have shown that immunological reaction can be initiated by trauma to an anatomic location. In some cases the tumor SR became evident only after the tissue biopsy, observation that leads to the option that immune response to the surgical procedure seems to be a plausible contributor to the SR. Para-neoplastic sensorimotor neuropathy (PNS) has been suggested as a mechanism of SCLC and NSCLC SR. Specific anti-neuronal auto-antibodies, anti-Hu antibodies, react both to the tumor and nervous system, in patients with sensorimotor neuropathy, and this inflammatory response has been associated with the antitumor immune response. Many cases of SCLC SR have been escorted by neurological symptoms, but no neurological abnormalities were observed. However, the real association between PNS, Hu-antibody and SR of lung cancer still needs to be clarified by further evidence. It has also been recorded that bronchoscopy contributed to SR of lung cancers. Diverse case reports have recorded patients with advanced, poorly differentiated NSCLC (highly expressing programmed death ligand-1 [PD-L1]) that progressed despite multiple cycles of chemotherapy but then spontaneously remitted, patients with lung squamous cell carcinoma who experienced SR following biopsy without other therapeutic intervention, and patients with lung adenocarcinoma that spontaneously remitted. Almost all case reports described SR of an untreated lung cancer and were diagnosed and histologically confirmed.

Anti-Hu Encephalitis Associated With Small Cell Lung Cancer,A Case Report

Paraneoplastic limbic encephalitis (PLE) is a rare neurologic that can be a manifestation of lung cancer. These manifestations are frequently seen in patients diagnosed with small cell lung cancer (SCLC), as in our case. This is a case report of a 66-years-old woman, with SCLC that has been diagnosed due to paraneoplastic encephalitis staining positive for anti-Hu antibodies. Sometimes differential diagnosis involves endocrinopathies and other neurological conditions, so many specialists must co-operate in each patient

'Primary progressive multiple sclerosis overlapping with anti-GAD and anti-Hu antibodies positive neurological syndromes' - clinical considerations.

'Primary progressive multiple sclerosis overlapping with anti-GAD and anti-Hu antibodies positive neurological syndromes' - clinical considerations.

Response relating to the article 'Primary progressive multiple sclerosis overlapping with anti-GAD and anti-Hu antibodies positive neurological syndromes'.

Response relating to the article 'Primary progressive multiple sclerosis overlapping with anti-GAD and anti-Hu antibodies positive neurological syndromes'.

Interaction of Anti-Yo and anti-Hu Antibodies with Neurons in Living Mice Following Intracranial Injection or Infusion: Demonstration of Neuronal Antibody Uptake and Early Detection of Neuronal Death (S41.004)

Interaction of Anti-Yo and anti-Hu Antibodies with Neurons in Living Mice Following Intracranial Injection or Infusion: Demonstration of Neuronal Antibody Uptake and Early Detection of Neuronal Death (S41.004)

Anti-Hu Antibody-Mediated Myelopathy Associated with Gastric Adenocarcinoma

Anti-Hu antibody causes paraneoplastic syndrome of the nervous system. Most of the anti-Hu antibodies are found with small cell lung cancer, but can rarely be found with other cancers such as non-small cell lung cancer, prostate cancer, and breast cancer. We report a 57-year-old male patient with advanced gastric adenocarcinoma who had paresthesia and limb ataxia. Electrophysiologic study and imaging showed peripheral neuropathy accompanied with myelitis. Anti-Hu antibody was detected in the patient’s serum, leading to the diagnosis of paraneoplastic syndrome.

Paraneoplastic and Other Autoimmune Encephalitides: Antineuronal Antibodies, T Lymphocytes, and Questions of Pathogenesis.

Autoimmune and paraneoplastic encephalitides represent an increasingly recognized cause of devastating human illness as well as an emerging area of neurological injury associated with immune checkpoint inhibitors. Two groups of antibodies have been detected in affected patients. Antibodies in the first group are directed against neuronal cell surface membrane proteins and are exemplified by antibodies directed against the N-methyl-D-aspartate receptor (anti-NMDAR), found in patients with autoimmune encephalitis, and antibodies directed against the leucine-rich glioma-inactivated 1 protein (anti-LGI1), associated with faciobrachial dystonic seizures and limbic encephalitis. Antibodies in this group produce non-lethal neuronal dysfunction, and their associated conditions often respond to treatment. Antibodies in the second group, as exemplified by anti-Yo antibody, found in patients with rapidly progressive cerebellar syndrome, and anti-Hu antibody, associated with encephalomyelitis, react with intracellular neuronal antigens. These antibodies are characteristically found in patients with underlying malignancy, and neurological impairment is the result of neuronal death. Within the last few years, major advances have been made in understanding the pathogenesis of neurological disorders associated with antibodies against neuronal cell surface antigens. In contrast, the events that lead to neuronal death in conditions associated with antibodies directed against intracellular antigens, such as anti-Yo and anti-Hu, remain poorly understood, and the respective roles of antibodies and T lymphocytes in causing neuronal injury have not been defined in an animal model. In this review, we discuss current knowledge of these two groups of antibodies in terms of their discovery, how they arise, the interaction of both types of antibodies with their molecular targets, and the attempts that have been made to reproduce human neuronal injury in tissue culture models and experimental animals. We then discuss the emerging area of autoimmune neuronal injury associated with immune checkpoint inhibitors and the implications of current research for the treatment of affected patients.