Antibody-positive autoimmune encephalitis and paraneoplastic neurological syndrome: A Swedish case series.

OBJECTIVE: This study aimed to explore the clinical characteristics and temporal disease course of patients with autoimmune encephalitis (AE) and paraneoplastic neurological syndrome (PNS) in Sweden. METHODS: Thirty-seven antibody-positive AE and PNS cases were identified in the Healthcare region Mid Sweden between 2015 and 2019. Clinical data were collected through a retrospective review of electronic health records. Patients were divided into three subgroups based on antibody type: neuronal surface antibodies (NSAbs), onconeural antibodies, and anti-GAD65 antibodies. RESULTS: Nineteen patients had NSAbs, 11 onconeural antibodies, and seven anti-GAD65 antibodies. Anti-LGI1 and anti-NMDAR were the most frequently detected NSAbs, with anti-NMDAR cases having an older-than-expected age distribution (median age 40, range 17-72). Only 11 of 32 (30%) of patients had findings suggesting encephalitis on initial MRI, but 28 of 31 (90%) had pathological findings on initial cerebrospinal fluid analysis. All patients but one had abnormal EEG findings. Median time to immunotherapy was comparable among the three subgroups, whereas patients with anti-LGI1, anti-CASPR2, and anti-IgLON5 had an eightfold longer time to immunotherapy than anti-NMDAR and anti-GABA-B (p = .0016). There was a seasonal variation in onset for patients with non-tumor-related NSAbs and anti-GAD65 antibodies, with most patients (72%) falling ill in spring or summer. CONCLUSION: Swedish patients with AE and PNS had similar clinical characteristics as previously described cohorts from other geographical regions except for anti-NMDAR encephalitis, with older onset than expected. The onset of non-tumor-related AE occurred predominantly in the warm seasons, and AE with a more insidious onset was associated with delayed treatment initiation.

Paraneoplastic cochleovestibulopathy: clinical presentations, oncological and serological associations.

OBJECTIVE: Cochleovestibulopathy is a distinguishable paraneoplastic phenotype. In this study, we evaluate clinical presentation, serological/cancer associations and outcomes of paraneoplastic cochleovestibulopathy. METHODS: Retrospective chart review of patients with hearing impairment and/or vestibulopathy who underwent serological evaluations for paraneoplastic antibodies between January 2007 and February 2021 was performed. RESULTS: Twenty-six patients were identified (men, n=23; median age, 45 years, range: 28-70). Biomarkers detected included: KLHL11-IgG| |(n=20,| |77% (coexisting LUZP4-IgG, n=8)),| ||ANNA1-IgG| | |(n=3,| |12%),| |amphiphysin-IgG|| |(n=2,| |8%)| |and| |LUZP4-IgG|| |(n=1,| |4%). Most common neoplastic association was |testicular|/|extra-testicular| |seminoma| | (n=13,| |50%).|| Hearing| impairment (bilateral, 62%) was |present| |in| |all| |patients.| |Fifteen patients (58%) had cochleovestibular dysfunction as their initial presentation before rhombencephalitis/encephalomyelitis manifestations (hearing loss, four; acute vertigo, eight; both, three). |Brain| |MRI| |demonstrated| |internal| |auditory| |canal| |enhancement| |in| |four |patients.| Audiometry commonly revealed severe-profound bilateral sensorineural hearing loss. Most patients |had| a refractory course |despite| |immunotherapy| |and/or| |cancer| |treatment|. CONCLUSION: Cochleovestibulopathy commonly presents with rapidly progressive bilateral hearing loss and/or acute vertigo. However, in some patients, these symptoms present along with or following brainstem/cerebellar manifestations. KLHL11-IgG and seminoma are the most common serological and cancer associations, respectively. Recognition of this phenotype may aid in earlier diagnosis of paraneoplastic autoimmunity and associated cancer.

Gastrointestinal dysmotility in a patient with advanced lung cancer: paraneoplastic or drug-induced?

A 75-year-old man was hospitalised for bronchoscopy with biopsy due to a suspicious pulmonary mass at chest tomography. He had significant dyspnoea, constipation, nausea, vomiting, anorexia and a 33% loss of weight in the past 3 months. Biopsy revealed a pulmonary squamous cell carcinoma, which was inoperable. Tramadol used at home for 3 months was replaced by morphine on admission. The patient remained constipated despite prokinetics and laxatives, leading to the diagnostic hypothesis of paraneoplastic motility disorder and opioid-induced constipation. Abdominal tomography ruled out the possibility of mechanical obstruction. As complications, the patient presented superior vena cava syndrome and opioid (morphine) intoxication. The patient died a few days later. The management of this case highlights the importance of multidisciplinary care and the challenges of palliative oncology care. Paraneoplastic motility disorder must always be considered among the mechanisms of intestinal dysfunction in patients with advanced oncological disease.

A Case of Paraneoplastic Myoclonus Attributed to Non-Small Cell Lung Cancer.

Background: It is well known that myoclonus can be a paraneoplastic manifestation of underlying malignancy. Case Report: A 78-year-old male diagnosed with papillary variant non-small cell lung cancer (NSCLC) presented with tremulousness that rapidly evolved into severe, diffuse myoclonus with prominent palatal involvement requiring intubation. The generalized myoclonus resolved with on levetiracetam, chemotherapy and immune modulation. While low titer positive P/Q type calcium channel autoantibodies were detected, it's etiologic relevance is unclear. Discussion: This case highlights a rare neurologic paraneoplastic presentation of papillary NSCLC. It also illustrates the importance of monitoring airway safety when myoclonus is generalized. Highlights: A new, rare paraneoplastic presentation of papillary variant non-small cell lung adenocarcinoma is described. The patient presented with severe diffuse myoclonus with prominent palatal involvement without encephalitis that responded to a combination of chemotherapy, immune modulation, and levetiracetam. No clear causal antibody was found.

Autonomic Dysfunction is Associated with Increased Cardiometabolic Risk in Patients with Childhood-Onset Craniopharyngioma.

Patients with craniopharyngioma are susceptible to autonomic dysfunction as a result of hypothalamic damage. We evaluated indices of heart rate variability (HRV) in patients with childhood-onset craniopharyngioma to investigate autonomic function and its relationship with components of the metabolic syndrome (MetS). This cross-sectional, case-only study included 53 patients (10-30 years of age). We measured the standard deviation of all normal R-R intervals (SDNN) and total power indicating overall HRV, the root-mean square of the difference of successive R-R intervals (RMSSD) and high frequency indicating parasympathetic modulation, and low frequency. These indices were compared according to the presence of the MetS. During the mean 10.8 years of follow-up, 25% of patients were diagnosed with the MetS. Patients with the MetS showed significantly lower levels of SDNN (29.0 vs. 40.6 ms), total power (416.1 vs. 1129.6 ms2), RMSSD (20.1 vs. 34.5 ms), high frequency (94.7 vs. 338.5 ms2), and low frequency (94.5 vs. 289.4 ms2) than those without (p <0.05, for all). Individual components of the MetS including insulin resistance, serum triglycerides levels, and systolic blood pressure were inversely associated with SDNN, total power, RMSSD and high frequency. Higher overall variability and parasympathetic modulation were related to decreased odds ratios for having the MetS (OR 0.91, p=0.029 for SDNN; OR 0.91, p=0.032 for total power). In conclusion, autonomic dysfunction, as evidenced by reduced HRV indices, is associated with increased cardiometabolic risk in patients with childhood-onset craniopharyngioma.

Pediatric Paraneoplastic Necrotizing Encephalitis Associated With Acute Lymphoblastic Leukemia.

BACKGROUND: Paraneoplastic encephalitis encompasses a diverse spectrum of neurological disorders associated with a variety of pediatric tumor types. METHODS: We describe a seven-year-old boy with paraneoplastic necrotizing encephalitis associated with precursor B-cell acute lymphoblastic leukemia. RESULTS: The initial presentation involved acute-onset upper extremity weakness, seizure-like activity, and agitation. Extensive evaluation revealed pancytopenia, elevated protein in the cerebrospinal fluid, and normal magnetic resonance imaging (MRI) consistent with a clinical diagnosis of encephalitis of presumed viral etiology. He was treated with antimicrobials and intravenous immunoglobulin and returned to his neurological baseline before discharge. One month later, he was diagnosed with precursor B-cell acute lymphoblastic leukemia. Before chemotherapy initiation, he again became encephalopathic. Repeat cerebrospinal fluid evaluation showed elevated protein, and MRI revealed findings consistent with diffuse necrotizing encephalitis. He received standard chemotherapy as well as immunotherapy with intravenous immunoglobulin and plasmapheresis, with resolution of MRI abnormalities and improvement in neurological status. At six years postpresentation, he is in remission for acute lymphoblastic leukemia, without significant neurocognitive deficits and mild right spastic hemiparesis. CONCLUSION: This is the first report of paraneoplastic encephalitis associated with pediatric leukemia. A hematologic malignancy should be considered in the differential diagnosis of paraneoplastic encephalitis.

Treatment of Movement Disorder Emergencies in Autoimmune Encephalitis in the Neurosciences ICU.

Immune response against neuronal and glial cell surface and cytosolic antigens is an important cause of encephalitis. It may be triggered by activation of the immune system in response to an infection (para-infectious), cancer (paraneoplastic), or due to a patient's tendency toward autoimmunity. Antibodies directed toward neuronal cell surface antigens are directly pathogenic, whereas antibodies with intracellular targets may become pathogenic if the antigen is transiently exposed to the cell surface or via activation of cytotoxic T cells. Immune-mediated encephalitis is well recognized and may require intensive care due to status epilepticus, need for invasive ventilation, or dysautonomia. Patients with immune-mediated encephalitis may become critically ill and display clinically complex and challenging to treat movement disorders in over 80% of the cases (Zhang et al. in Neurocrit Care 29(2):264-272, 2018). Treatment options include immunotherapy and symptomatic agents affecting dopamine or acetylcholine neurotransmission. There has been no prior published guidance for management of these movement disorders for the intensivist. Herein, we discuss the immune-mediated encephalitis most likely to cause critical illness, clinical features and mechanisms of movement disorders and propose a management algorithm.

Parkinsonism in autoimmune diseases.

Parkinsonism can be manifested and complicate either systemic or organ-specific autoimmune diseases. Even though it is a rare co-morbidity, it merits attention from clinicians as it affects the quality of life of patients. In systemic autoimmune diseases such as systemic lupus erythematosus, antiphospholipid syndrome and Sjogren's syndrome reported cases of parkinsonism are attributed to the underlying disease and its mechanisms, whether this is brain vasculitis or immune complexes. Regarding antibody-mediated autoimmune neurological disorders, parkinsonism is, in most cases, a manifestation within the spectrum of each disorder and is attributed to the action of humoral and cellular immunity in brain regions such as the basal ganglia. Depending on the pathophysiology, immunotherapy can be effective, while Parkinson's specific therapies are usually less effective.

Clinical Heterogeneity in Patients with Glutamate Decarboxylase Antibody.

OBJECTIVE: To explore the diversity and clinical features of anti-glutamate decarboxylase (GAD) antibody-associated neurological diseases. METHODS: Clinical data of a series of 5 patients positive for anti-GAD antibodies were retrospectively analyzed. RESULTS: All 5 patients were female, with a median age of 41.5 years (range 19-60 years). Their neurological symptoms included stiff-person syndrome (SPS), encephalitis, myelitis, cramp, visual loss, and paresthesia. Three patients (60%) were diagnosed with tumors, 2 cases of thymic tumor and 1 of breast cancer. On immunohistochemistry for tumor pathology, expression of GAD65 was found only in 1 patient. Four patients (80%) had abnormal brain MRI findings. All patients received immunotherapy and improved significantly after treatment, but 4 (80%) then experienced a relapse. CONCLUSIONS: Neurological manifestations in anti-GAD-positive patients are diverse and include SPS, encephalitis, myelitis, cramp, visual loss, and paresthesia.

Neurological autoimmune disorders with prominent gastrointestinal manifestations: A review of presentation, evaluation, and treatment.

BACKGROUND: The identification of autoantibodies directed against neuronal antigens has led to the recognition of a wide spectrum of neurological autoimmune disorders (NAD). With timely recognition and treatment, many patients with NAD see rapid improvement. Symptoms associated with NAD can be diverse and are determined by the regions of the nervous system affected. In addition to neurological symptoms, a number of these disorders present with prominent gastrointestinal (GI) manifestations such as nausea, diarrhea, weight loss, and gastroparesis prompting an initial evaluation by gastroenterologists. PURPOSE: This review provides a general overview of autoantibodies within the nervous system, focusing on three scenarios in which nervous system autoimmunity may initially present with gut symptoms. A general approach to evaluation and treatment, including antibody testing, will be reviewed.

Motor neuron involvement in anti-Ma2-associated paraneoplastic neurological syndrome.

OBJECTIVE: To present clinical, radiological, and pathological features of a cohort of patients with motor neuron involvement in association with anti-Ma2 antibodies (Ma2-Ab). METHODS: Retrospective case-series of patients with definite paraneoplastic neurological syndrome (PNS) and Ma2-Ab, and cases identified from a review of the literature. RESULTS: Among 33 Ma2-Ab patients referred between 2002 and 2016, we retrospectively identified three patients (9.1%) with a motor neuron syndrome (MNS). Seven additional cases were retrieved among the 75 Ma2-patients reported in the literature (9.3%). A total of ten patients are, therefore, described herein. MNS was evident as combined upper and lower MNS in four patients, isolated upper MNS in two, and isolated lower MNS in one; three patients were diagnosed with myeloradiculopathy. The most common MNS signs/symptoms were: hyperreflexia (80%), proximal weakness (60%), proximal upper-limb fasciculations (50%), head drop (40%), and dysarthria/dysphagia (30%). Brain MRI abnormalities included bilateral pyramidal tract T2-weighted/FLAIR hyperintensities (three patients). Spine MRI found bilateral, symmetric, T2-weighted signal abnormalities in the anterior horn in two patients. CSF examination was abnormal in nine patients. Cancer was found in seven patients (four testicular, two lung, and one mesothelioma). Eight patients underwent first-line immunotherapy. Second-line immunotherapy was adopted in all our patients and in none of those identified in the literature. Motor improvement was observed in 33% of our patients, and 20% in the literature series. CONCLUSIONS: Motor neuron involvement could complicate Ma2-Ab-associated PNS in almost 10% of patients and must be carefully studied to adapt treatment. This disorder differs from amyotrophic lateral sclerosis.

Isolated seizures are a common early feature of paraneoplastic anti-GABAB receptor encephalitis.

OBJECTIVE: To report the clinical features and long-term outcome of 22 newly diagnosed paraneoplastic patients with GABAB receptor antibodies (GABABR-Abs). METHODS: Retrospective clinical study of CSF-confirmed cases of GABABR-Abs encephalitis. RESULTS: We identified 22 patients (4 female) with GABABR-Abs, with a median age of 64 years (range 55-85). All were paraneoplastic: 20 small-cell lung cancer, one malignant thymoma, and one uncharacterized lung mass. The most frequent first symptom was the isolated recurrent seizures without cognitive inter-ictal impairment in 17 patients (77%). In the other, three presented the first behavioral disorders and two presented de novo status epilepticus (SE). After a median delay of 10 days (range 1-30), the recurrent seizures' phase was followed by an encephalitic phase characterized by confusion in 100% of cases and SE in 81% (n = 17), with 53% (n = 9) non-convulsive SE. Dysautonomic episodes were frequent (36%, n = 8, bradycardia and central apnea) and killed three patients. CSF study was abnormal in 95% of the cases (n = 21). At the encephalitic phase, MRI showed a temporal FLAIR hypersignal in 73% (n = 16) of the cases. First-line immunotherapy was initiated after a median delay of 26 days (range 6-65) from disease onset, and a partial response was observed in 10 out of 20 patients (50%). There was no complete response. Two years after onset, a massive anterograde amnesia affected all still alive patients. Nine patients died from cancer progression (median survival: 1.2 years). CONCLUSION: Paraneoplastic GABABR-Abs encephalitis is characterized by a stereotype presentation with an epilepsy phase before an encephalitic phase with dysautonomia. The functional prognosis is poor.

Paraneoplastic Neuromyelitis Optica Spectrum Disorder: A single center cohort description with two cases of histological validation.

BACKGROUND: Paraneoplastic syndromes are remote effects of cancer caused by an autoimmune response triggered by tumor cells. Paraneoplastic Neuromyelitis Optica Spectrum Disorders (NMOSD) has been previously described, but the underlying mechanism for these rare cases is not well characterized. This paper presents a newly described case series of paraneoplastic NMOSD, including 2 new histological types of cancer and histological validation. METHODS: The UBC NMO clinic database was surveyed and identified 6 patients with paraneoplastic NMOSD. In 2 cases, aquaporin-4 (AQP4) immunoreactivity was assessed on patients' tumor specimens. RESULTS: The mean age at NMOSD diagnosis was 56 years old and 5/6 patients were older than 50 years old. 4/6 patients with paraneoplastic NMOSD have positive AQP4 antibodies. The median time between NMOSD and cancer was 12 months. Two new cancer types- serous ovarian carcinoma and adrenocortical carcinoma - were found in paraneoplastic NMOSD cases. A serous ovarian carcinoma and a thymoma, found in patients with AQP4 serological evidence, showed a positive reactivity to AQP4 immunostaining. CONCLUSIONS: Our findings will increase the recognition of NMOSD as a paraneoplastic syndrome. Cancer cells can express AQP4, increasing the likelihood of a direct mechanism between cancer cells and the development of NMOSD in paraneoplastic cases.

Breast cancer-related paraneoplastic neurologic disease.

PURPOSE: Paraneoplastic neurologic disease (PND) is an aberrant immune-mediated response against the nervous system triggered by malignancy. Given the rarity, a paucity of data describing breast cancer-related PND (BC-PND) exists; we sought to further examine this specific patient population. METHODS: We retrospectively identified patients at our institution from 1997 to 2016 with BC-PND. Retrospective review with a descriptive analysis determined factors associated with PND and BC, which were compared to national breast cancer median of age (61 years) and average stage at diagnosis (60% local disease). RESULTS: BC-PND was diagnosed in 56 female patients at a median age of 52.8 years. Only 20% of invasive cancer patients had local disease. The majority of patients were hormone receptor positive and Her2 negative. Neurological symptoms presented prior to BC diagnosis in 57.1% of patients. Of all patients, 30 (53.6%) had autoantibodies detected: Purkinje Cell Cytoplasmic Autoantibody Type-1 (PCA-1[anti-Yo]), n = 10; amphiphysin-IgG, n = 9; Anti-Neuronal Nuclear Autoantibody Type-2 (ANNA-2[anti-Ri]), n = 5; and others, n = 6. The most common neurologic findings were cerebellar ataxia, myelopathy, and myopathy. Immunotherapy benefit was found to be robust (21.6%), mild to moderate (52.9%), absent (17.6%), or indeterminate (7.8%). CONCLUSIONS: PND symptoms often presented prior to BC diagnosis, with the BC biologic subtype characteristics typical of the general BC population. BC diagnoses were often made at younger ages than that of the general BC population and with later-stage disease. Roughly 75% of patients benefited from immunotherapy. These data provide helpful information to providers treating this population of patients.

Autoimmune Encephalitides: A Broadening Field of Treatable Conditions.

BACKGROUND: Neurology has been continuously transforming by the refinement of molecular diagnostics and the development of disease-modifying treatments. The discovery of new antibody markers has elucidated the pathogenesis, provided the means of diagnostics, and offered cure or treatment for several immune-mediated neurological and neuropsychiatric disorders. The identification of pathogenic and marker autoantibodies has also facilitated defining the associated phenotypic spectra and the overlap among the phenotypes linked to individual immune markers. REVIEW SUMMARY: This survey presents the list of currently known autoimmune encephalitis entities along with the associated marker autoantibodies, highlights the phenotypic and immune pathogenic relationships, calls attention to the recently described rare syndromes, discusses the biological significance of the autoantibodies and targeted molecules, points out the potential postinfectious origin of immune pathogenesis in several of the disorders, and directs the readers to the latest diagnostic guidelines as well as to the generally used treatment approaches. CONCLUSIONS AND FUTURE DIRECTIONS: Owing to the successful and usually combined use of various methods to detect serum and cerebrospinal fluid autoantibodies on rodent brain sections, in primary neuronal cell culture, in immune precipitation, and cell-based assays, or in other antigen-specific immune assays (Western blot, enzyme-linked immunosorbent assay, and radioimmune assay), the subgroup of antibody marker-negative autoimmune encephalopathy syndromes is contracting, whereas the numbers of entities within the overall group are expanding. Recognition of the correct diagnosis is becoming increasingly rewarding not only for neurologists, but also for pediatric neurologists and psychiatrists.

Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy: A Novel Meningoencephalomyelitis.

IMPORTANCE: A novel astrocytic autoantibody has been identified as a biomarker of a relapsing autoimmune meningoencephalomyelitis that is immunotherapy responsive. Seropositivity distinguishes autoimmune glial fibrillary acidic protein (GFAP) meningoencephalomyelitis from disorders commonly considered in the differential diagnosis. OBJECTIVE: To describe a novel IgG autoantibody found in serum or cerebrospinal fluid that is specific for a cytosolic intermediate filament protein of astrocytes. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of the medical records of seropositive patients identified in the Mayo Clinic Neuroimmunology Laboratory from October 15, 1998, to April 1, 2016, in blinded comprehensive serologic evaluation for autoantibody profiles to aid the diagnosis of neurologic autoimmunity (and predict cancer likelihood). MAIN OUTCOMES AND MEASURES: Frequency and definition of novel autoantibody, the autoantigen's immunochemical identification, clinical and magnetic resonance imaging correlations of the autoantibody, and immunotherapy responsiveness. RESULTS: Of 103 patients whose medical records were available for review, the 16 initial patients identified as seropositive were the subject of this study. Median age at neurologic symptom onset was 42 years (range, 21-73 years); there was no sex predominance. The novel neural autoantibody, which we discovered to be GFAP-specific, is disease spectrum restricted but not rare (frequency equivalent to Purkinje cell antibody type 1 [anti-Yo]). Its filamentous pial, subventricular, and perivascular immunostaining pattern on mouse tissue resembles the characteristic magnetic resonance imaging findings of linear perivascular enhancement in patients. Prominent clinical manifestations are headache, subacute encephalopathy, optic papillitis, inflammatory myelitis, postural tremor, and cerebellar ataxia. Cerebrospinal fluid was inflammatory in 13 of 14 patients (93%) with data available. Neoplasia was diagnosed within 3 years of neurologic onset in 6 of 16 patients (38%): prostate and gastroesophageal adenocarcinomas, myeloma, melanoma, colonic carcinoid, parotid pleomorphic adenoma, and teratoma. Neurologic improvement followed treatment with high-dose corticosteroids, with a tendency of patients to relapse without long-term immunosuppression. CONCLUSIONS AND RELEVANCE: Glial fibrillary acidic protein-specific IgG identifies a distinctive, corticosteroid-responsive, sometimes paraneoplastic autoimmune meningoencephalomyelitis. It has a lethal canine equivalent: necrotizing meningoencephalitis. Expression of GFAP has been reported in some of the tumor types identified in paraneoplastic cases. Glial fibrillary acidic protein peptide-specific cytotoxic CD8+ T cells are implicated as effectors in a transgenic mouse model of autoimmune GFAP meningoencephalitis.

Is peripheral paraneoplastic neurological syndrome possible in primary brain tumors?

INTRODUCTION: Systemic malignant diseases cause the induction of autoimmunity, for example, paraneoplastic syndromes. There are no proofs of paraneoplastic syndromes in primary brain tumors. The aim of the study was to evaluate the involvement of the peripheral nervous system, together with an assessment of onconeuronal and antineural antibodies as indicators of humoral immune response against nervous system in patients with primary brain tumors. MATERIALS AND METHODS: Clinical examinations, electrophysiological studies of peripheral nerves (motor and sensory conduction velocity studies, conduction velocity distribution tests, thermal and vibratory quantitative sensory tests, and sympathetic skin response tests) and muscles, blood sampling collection (assessment of onconeuronal, and antineural antibodies) were performed on 33 patients with newly recognized primary brain tumors within 2-4 days after their admission to our department. RESULTS: We revealed statistically significant changes of peripheral nerves, more pronounced in the peroneal nerve in standard and conduction velocity distribution tests, as well as in sympathetic skin responses. We revealed significantly higher vibratory thresholds, and pain thresholds for cold and warm in the upper and lower limbs in the study group than in the controls. In five patients, we have identified anti-neuroendothelium, anti-GFAP, anti-MAG, anti-PCNA, and anti-Ro52 antibodies. CONCLUSIONS: In patients with primary brain tumors, electrophysiological changes in peripheral nerves, together with the presence of the antineural antibodies suggest an autoimmune humoral response, and make the diagnosis of paraneoplastic neurological syndrome possible.

A Rare Case of Childhood Stiff Person Syndrome Associated With Pleuropulmonary Blastoma.

INTRODUCTION: Stiff person syndrome is a rare autoimmune, neurological disorder characterized by progressive rigidity and episodic painful spasms, predominantly affecting the proximal limbs and axial muscles, and leading to progressive disability. We report the case of a child who developed symptoms compatible with stiff person syndrome during treatment for pleuropulmonary blastoma. PATIENT DESCRIPTION: A 3-year, 5-month-old girl was admitted for gradually worsening postural tremor, painful spasms, and generalized stiffness. Since the age of 3 years, she had been on adjuvant chemotherapy for pleuropulmonary blastoma before surgical resection. Brain magnetic resonance imaging and electroencephalographic findings were normal. Although serologic tests for autoimmune disease, including paraneoplastic antibodies and antiglutamic acid decarboxylase antibodies, were unremarkable, her findings were attributed to a paraneoplastic syndrome based on her clinical features and medical history. However, following the planned pulmonary lobectomy, her symptoms were paradoxically aggravated, with continuous motor unit potential at rest on electromyography, which occurs in stiff person syndrome. She gradually improved during postadjuvant chemotherapy with simultaneous immunotherapy including intravenous immunoglobulins and methylprednisolone, and she had recovered completely when evaluated at the 22-month follow-up visit after completion of her treatment for pleuropulmonary blastoma. CONCLUSION: We present the first documented child with stiff person syndrome associated with pleuropulmonary blastoma. The marked clinical improvement following chemotherapy for pleuropulmonary blastoma was yet more proof of the pleuropulmonary blastoma-related stiff person syndrome. In children with a malignancy and stiff person syndrome, a paraneoplastic syndrome should be considered and the treatment for the malignancy must be undertaken.