Prodromal Illness Research Articles

Not hysteria: ovarian teratoma-associated anti-N-methyl-d-aspartate receptor encephalitis

We report a case of a 33-year-old nulliparous woman who, following a short prodromal illness, experienced a series of psychiatric and behavioural symptoms. These included states of terror, insomnia, delirium, self-harm and suicidal ideation, facial dyskinesias, verbigeration, cognitive impairment, reduced responsiveness, violence and paranoia. A diagnosis of anti-N-methyl-d-aspartate (NMDAR) encephalitis was made 50 days after symptom onset. Early tumour removal is associated with an improved prognosis and a laparoscopic oophorectomy was performed following detection of a dermoid cyst. Within 24 hours of the operation there was marked improvement in cognitive function and appetite.

C6 Not all IRIS's are equal: a case of sudden death

BackgroundMyocarditis is a well-recognised complication of HIV infection but is seldom observed in clinical practice in the UK. Additionally, myocarditis has been associated with sudden unexplained death in the general...

Acute Disseminated Encephalomyelitis in Children: A Single Institution Experience of 28 Patients

The aim of this study is to describe the clinical, laboratory, and neuroimaging features, treatment and outcome of acute disseminated encephalomyelitis (ADEM) in Taiwanese children to compare with two series from United States of America and Japan. We retrospectively reviewed the medical records and magnetic resonance images of 28 children, 23 boys and 5 girls, with ADEM between January 2001 and December 2009. Their mean age at disease onset was 6 years 9 months. Twenty four children experienced a prodromal illness. There was no special seasonal distribution in our patients. They presented mostly with impaired consciousness and headache. Cerebrospinal fluid samples of 21 patients were analyzed and none showed intrathecal oligoclonal bands. Magnetic resonance imaging showed variable findings: lesions with abnormal signal changes frequently found in the subcortical white matter of frontal and parietal lobes. No patient showed cortical gray matter involvement. We also found a high rate of deep gray matter involvement including thalami and basal ganglia. Treating with steroids was usually associated with a rapid recovery and both intravenous high dose methylprednisolone and dexamethasone had the same effect. All patients survived. Twenty three patients recovered completely with only mild sequelae in the remaining five children.

Clinical Reasoning: A 34-year-old man with recurrent limb weakness

A 34-year-old healthy man presented with 3 weeks of progressive bilateral arm weakness. He first noticed weakness while combing his hair and getting dressed. His symptoms were preceded by transient paresthesia in all 5 fingertips of both hands. Over the next 2 weeks, his weakness progressed slowly and spread to his forearms and hands. He never felt numbness or tingling in the feet. There was no visual disturbance, dysphagia, dysarthria, or bladder or bowel disturbance. There was no prodromal illness or vaccination. He took no medications and did not drink, smoke, or use drugs. Familial history was unremarkable. His general examination, including supine and erect blood pressure and pulse, was normal. The cranial nerves were intact. Strength was 3/5 in both deltoids and 4/5 in remaining muscles of both upper extremities. Neck flexor, extensor, and bilateral lower extremity muscles demonstrated normal muscle strength. Tendon reflexes were all absent apart from reduced bilateral brachioradialis and left triceps reflexes. Sensory tests with pin, cold, vibration, and proprioception had normal results. The rest of his examination, including gait, was normal. ### Question for consideration: 1. What is your differential diagnosis at this stage? This patient presented with progressive bilateral arm weakness. The sensory symptoms were subjective, minimal, and resolved eventually prior to treatment. Although the pattern of weakness suggests a myopathy, the clinical examination is more consistent with a motor neuropathy. The absence of the reflexes, in particular in the legs which were strong, makes the diagnosis of myopathy unlikely. Patients with Lambert-Eaton myasthenic syndrome (LEMS) can have absent reflexes which may reappear after exercise, but frequently have autonomic symptoms with weakness mainly in the legs. The differential diagnosis of an acute motor neuropathy includes the following1: 1. Idiopathic inflammatory causes such as Guillain-Barre syndrome (GBS), multifocal motor neuropathy (MMN), acute onset chronic inflammatory demyelinating polyneuropathy (CIDP), …

Hematopoietic Radiation Syndrome in the Gottingen Minipig

Additional large animal models for the acute radiation syndrome (ARS) would facilitate countermeasure development. We demonstrate here that Gottingen minipigs develop hematopoietic ARS symptoms similar to those observed in canines, non-human primates (NHPs) and humans. Dosimetry for whole-body γ irradiation (0.6 Gy/min) was performed using electronic paramagnetic resonance (EPR) with alanine; National Institute of Standards and Technology (NIST)-calibrated alanine pellets and water-filled Plexiglas phantoms were used. After irradiations of 1.6-2.0 Gy, blood pancytopenia was observed for several weeks, accompanied by the characteristic ARS stages: prodromal symptoms, latent period, illness and recovery or morbidity. Morbidity occurred between days 14 and 27, with a preliminary LD(50/30) estimate between 1.7 and 1.9 Gy. The criterion of whether platelet counts were <200 × 10(3)/µl 7 days postirradiation predicted whether animals would survive in 18 out of 20 cases. The degree of granulocytosis 3 h postirradiation was inversely correlated with survival. Animals euthanized based on preset morbidity criteria displayed signs of multi-organ dysfunction, including widespread internal hemorrhage and alterations in organ function reflected in blood chemistry. Circulating C-reactive protein (CRP), a marker for inflammation, became elevated within hours after irradiation, subsided after several days, and increased again after 14 days. The results support further development of the Gottingen minipig as a model for ARS.

Sickness absence among cancer patients in the pre-diagnostic and the post-diagnostic phases of five common forms of cancer

The purpose of this study was to observe sickness absence before and after the cancer diagnosis among cancer patients with five common forms of cancer. Using cohort data, we observed sick leave in the pre- and post-diagnostic phase among patients with colon, rectal, breast, prostate, or lung cancer (n = 2,738). We also identified reference subjects without cancer (total n = 12,246) who were individually matched for age and gender for each specific cancer cohort in order to compare sickness absence between patients with a specific form of cancer and the background population without cancer. Lung cancer patients had the highest increase in sick days both pre- and post-diagnosis and prostate cancer patients had the lowest increase. Irrespective of the form of cancer, cancer patients had significantly more sick days in the post-diagnostic phase compared to their reference subjects, ranging from 5 (prostate cancer) to 12 times the amount of sick days (colon and lung cancer). One year post-diagnosis, less than half of the cancer patients were on sick leave, except for lung cancer patients where 63% were still on sick leave. Sick leave among cancer patients seems related not only to the cancer diagnosis and its treatment but also to the prodromal illness in the pre-diagnostic phase, especially for forms of cancer with heavier symptom burden such as colon and lung cancer. Although cancer results in substantial increase in sick leave, it is important to acknowledge that a major part of cancer patients return to work within 1year after the cancer diagnosis.

Spinal demyelination in acute disseminated encephalomyelitis: a risk factor for recurrent demyelination?

AimsAcute Disseminated Encephalomyelitis (ADEM) is a non-vasculitic, autoimmune demyelinating condition affecting predominantly cerebral white matter. ADEM commonly presents after a well defined pro-dromal febrile illness, and typically has a monophasic...

Not just a ‘simple stroke’

A 51-year-old man presenting with left arm weakness and slurred speech was referred to the acute medical team. Admission chest X-ray showed a cavitating lesion, which had not been present 2 weeks earlier. Systemic enquiry elicited a 2 month prodromal illness and back pain. Urgent CT of his head and chest revealed evidence of thoracic discitis spreading anteriorly into a pleural-based lung abscess and an intracerebral abscess causing his neurological deficit. He was transferred for urgent craniotomy and evacuation of a Streptococcus milleri abscess. Following several weeks of neurosurgical care and antibiotics he made a near full recovery.

Giving Bad News: A 13-Year Old With Acute Psychotic Symptoms and Catatonia

Scott, a 13-year 7-month old white male with no prior psychiatric history, presented to the emergency department after three days of decreased attention span and increased distractibility. An initial examination revealed that he was internally preoccupied (focused on responding to auditory hallucinations), displayed thought blocking (sudden interruption in the flow of his thoughts that prevented him from completing an idea), and he had periodic vague suicidal ideation due to intense guilt. He noted hearing two to three voices accusing him of being rude during an incident with a peer at school. He could not accept reassurance from his mother and grandparents that this incident had not actually occurred. Scott found evidence of his wrongdoing by misinterpreting words on signs and medical equipment that he felt indicated that others also knew of his malicious actions. A recent stressor included the conclusion of his active football season a day prior to the onset of his symptoms. Scott and his family denied a history of prodromal symptoms, mental or medical illnesses, including head injury. After a physical/neurological examination, a negative urine drug screen, and a normal complete blood count and metabolic panel, Scott was transferred to a psychiatric hospital. Scott returned to the emergency department two days later with worsening psychotic symptoms despite a trial of olanzapine. He had deteriorated dramatically from his initial presentation. He was now rigid, unable to speak, move his body, follow directions, eat, drink, or provide any additional history. After being admitted to the pediatrics floor an extensive medical workup was completed that included neurology and infectious disease consults, brain magnetic resonance imaging and angiography studies, a 24-hour electroencephalogram, lumbar puncture, urinalysis, complete blood count, comprehensive metabolic panel, ceruloplasm, anti-nuclear antibody, anti-DNAase, erythrocyte sedimentation rate, heavy metal screen, ammonia, rapid plasma reagin (RPR), and human immunodeficiency virus. All laboratory studies were normal.

Cerebrospinal Fluid Biomarkers in Mild Cognitive Impairment and Dementia

Given the magnitude of the public health problem of dementia in the elderly, there is a pressing need for research, development, and timely application of biomarkers that will identify latent and prodromal illness as well as dementia. Although identification of risk factors and neuroimaging measures will remain key to these efforts, this review focuses on recent progress in the discovery, validation, and standardization of cerebrospinal fluid (CSF) biomarkers, small molecules and macromolecules whose CSF concentration can aid in diagnosis at different stages of disease as well as in assessment of disease progression and response to therapeutics. A multimodal approach that brings independent information from risk factor assessment, neuroimaging, and biomarkers may soon guide physicians in the early diagnosis and management of cognitive impairment in the elderly.

Picture Quiz: ‘The Upper Hand’

A 76 year-old right-handed man presented acutely with a sudden onset of weakness affecting his right hand only. This happened while working in the garden. On detailed history taking, he denied any previous symptoms, trauma or prodromal illnesses. He denied any other neurological symptoms.

P01-384 - First episode psychoses psychometrical evaluation: a 24 months observational study with EASE and CAARMS

IntroductionDuring last few years psychiatric research focused her attention on early psychotic disorders, Ultra High Risk subjects, at risk mental states (ARMS) etc in order to determine clinical criteria of prodromal illness states.At the state of the art there is no evidence-based-approved scale for early diagnosis and the studies are for the most part dedicated to schizophrenia spectrum disorders.MethodologyAll the patients clinically remitted, suffered from a psychotic disorder during last 12 months (including schizophrenia spectrum, brief psychoses, psychotic bipolar illness) and high-risk subjects will be recruited and re-interviewed by expert clinicians. Psychometric classic scales (CGI, PANSS, BCIS, GAF) will be administered at the start of the study and after 2 years.During the interviews two psychopatological scales will be also administered to all subjects ; a phenomenologically oriented one, EASE scale (Parnas et al 2003) and CAARMS (McGorry, Barnaby Nelson 2006).During the 2 years observation, clinicians are requested to follow-up the patients and describe clinical and psychopathological modifications.ResultsThe preliminary results will be presented at the congress.ConclusionThis study focuses attention on psychotic illness dimension in order to better comprehend and grasp psychotic patients’ experience. A relationship between CAARMS-EASE score and clinical outcome is expected and will be discussed; thus could reinforce diagnostic and prognostic inference of early-diagnosis psychopatological scales. Limits of our study are the small sample and the brief temporal observation but are typical real-world conditions.

Posterior Reversible Encephalopathy Syndrome and Cerebral Vasculopathy Associated With Influenza A Infection

Influenza A infection can precipitate encephalopathy, encephalitis, or Reye syndrome with the development of cerebral edema in children and is associated with an increased incidence of stroke in adults. The mechanism of these events is poorly understood. Posterior reversible encephalopathy syndrome (PRES) is seen in association with infection/sepsis, and cerebral vasculopathy has been demonstrated in PRES. We describe a case of PRES that develops in association with influenza A. A normotensive 65-year-old woman presented with altered mentation and nausea in the setting of a viral prodromal illness ultimately confirmed as influenza A. Posterior reversible encephalopathy syndrome developed on the second day after admission. Catheter cerebral angiogram documented vasculopathy in PRES-involved regions with areas of focal vessel dilatation and string-of-bead appearance. The association between influenza A and PRES with documentation of cerebral vasculopathy suggests a common systemic vascular mechanism behind PRES and influenza-related encephalopathic edema and stroke.

Successful Treatment of Acute Autoimmune Limbic Encephalitis With Negative VGKC and NMDAR Antibodies

To describe a case of acute nonherpetic limbic encephalitis (LE) with negative testing for antibodies directed against onconeuronal and cell membrane antigens, including voltage-gated potassium channels and N-methyl-D-aspartate receptor, that showed a dramatic response to immune therapy. A 30-year-old woman manifested generalized seizures, altered consciousness, and memory impairment shortly after a prodromal viral illness. Few days later the patient developed a drug-resistant epileptic status. Electroencephalograph showed bitemporal slowing and paroxysmal slow wave bursts. Brain magnetic resonance imaging showed bilateral swelling in the medial temporal lobes. Cerebrospinal fluid analysis ruled out viral etiologies. A diagnostic search for cancer, including serum testing for known onconeuronal antibodies proved negative. Screening for cell membrane antigen antibodies, including voltage-gated potassium channels and N-methyl-D-aspartate receptor, was also negative. Suspecting an autoimmune etiology, we started an immunomodulatory treatment with intravenous immunoglobulin followed by a short course of oral prednisone, obtaining a full clinical recovery. Our report confirms previous observations of "seronegative" autoimmune LE, suggesting the presence of other, still unknown central nervous system antigens representing a target of a postinfectious, autoimmune response in these patients. Moreover, it emphasizes the importance of early recognition and treatment of acute autoimmune LE, to reduce the risk of intensive care unit-related complications and the occurrence of permanent cognitive or behavioral defects.

RESPONSE OF ANTI-NMDA RECEPTOR ENCEPHALITIS WITHOUT TUMOR TO IMMUNOTHERAPY INCLUDING RITUXIMAB

Paraneoplastic encephalitis with antibodies against NR1/NR2 heteromers of the NMDA receptor associates frequently with ovarian teratoma and has recently been established as a distinct clinical entity.1 Most patients are young women who develop a syndrome with prodromal cold-like illness, intractable seizures, psychosis, dyskinesia, and hypoventilation.1,2 However, about 40% of patients do not have a detectable tumor,3 and the treatment of these patients remains unclear. We report a patient with anti-NR1/NR2 encephalitis without teratoma who showed a nearly complete recovery after intensive immunotherapy including rituximab. ### Case report. A 42-year-old woman had cough and headache for 3 weeks. On the day before admission, she was found to be unresponsive for several minutes, and subsequently developed generalized seizures. On admission, her temperature was 38.2°C, and she had meningeal signs. CSF revealed mild pleocytosis (10/mm3) and slightly elevated protein concentration (45 mg/dL) with normal glucose concentration and IgG index. MRI (figure, A) and EEG were unremarkable. After the seizures were controlled, minimal disorientation was observed. Acyclovir and ceftriaxone were started. Figure MRI and FDG-PET studies of the brain (A) On day 2, the FLAIR MRI was normal. (B) On day 18, the FLAIR image revealed new high-intensity areas in the right temporal cortex, insula, parts of the frontal, parietal, and occipital cortices, and hippocampus. These findings were accompanied by mild edema. High-intensity areas were also observed in the left inferior temporal cortex and hippocampus. (C) On day 18, the gadolinium-enhanced T1-weighted …

Haematological malignancies presenting with acute liver injury: a single-centre experience

Early recognition and identification of the underlying cause of acute liver injury (ALI) is crucial in instituting medical treatment and assessing the need for liver transplantation. Haematological malignancies have been reported to present as ALI with progression to acute liver failure but experience is limited. Review our experience of ALI secondary to haematological malignancies. Patients admitted to the liver unit with ALI secondary to a haematological malignancy between 1996 and 2006 were identified. A retrospective review was made of their case notes and our database. Of the 752 cases of ALI, six cases of ALI secondary to haematological malignancy were identified. Common features were a prodromal illness (median duration of 5 weeks; range 2-6 weeks) and jaundice (median bilirubin 208 micromol/l; range 112-238 micromol/l). The majority of patients (5/6) had hepatomegaly. Liver biopsy was performed in two patients and confirmed the diagnosis in both cases. In other cases, the diagnosis was made following lymph node biopsy (1), bone marrow examination (2) or from post-mortem examination (1). Median time from jaundice to encephalopathy was 12 days; range 1-22 days. A single patient underwent liver transplantation but died in the immediate post-operative period. All patients died soon after admission with a median survival of 8 days (range 3-26 days). Haematological malignancy should be considered in ALI patients presenting with a prodromal illness, jaundice and hepatomegaly. Biopsy is essential to confirm the diagnosis but the benefit of definitive therapy such as chemotherapy and/or transplantation in this setting is unclear and survival is poor.

MOTIVATION AND PLEASURE IN THE SCHIZOPHRENIA SPECTRUM–FINDINGS FROM THE PRODROME

Background: Schizophreniais a chronic and debilitating illness that affects approximately one percent of the population. The symptoms of schizophrenia are typically thought of in separate domains, including positive symptoms (hallucinations and delusions), negative symptoms (diminished emotional expression and amotivation), and cognitive deficits. Importantly, the negative symptoms have been consistently found to adversely influence functional outcomes, in particular due to markedamotivation.^1 There have been suggestions that these individuals also experience deficits in the experience of pleasure, especially in their capacity to anticipate pleasure.^2 However, such investigations have not included the examination of these symptoms in those in the prodromal phase ofthis illness, a time that holds promise for early intervention and altering thecourse of schizophrenia.^3 Methods: In an effort to examine deficits in motivation and pleasure in the prodromal phase of schizophrenia, we have used an experience sampling method to assess “in the moment” motivation and pleasure in individuals at high risk of developing schizophrenia and healthy controls. Subjects completed baseline assessments including evaluation of their positive and negative symptoms. Subsequently, through the use of a personal digital assistant, subjects rated their motivation and experience of consummatory and anticipatory pleasure in their daily lives, multiple times over the course of four days. Results and Conclusions: Preliminary data will be presented, as well as the importance of these findings in the context of understanding the underlying pathobiology of this illness, and guiding our search for effective treatments to improvefunctional outcomes in schizophrenia.

Acute myocarditis secondary to Campylobacter jejuni enterocolitis

Myocarditis is a rare condition that can mimic an acute coronary syndrome (ACS). We present the case of a 24-year-old male with Noonan syndrome who presented with a diarrhoeal pro-dromal illness, acute onset chest pain, elevated cardiac biomarkers and an abnormal ECG with ST elevation in the absence of obstructive coronary artery disease. The patient had acute myocarditis secondary to Campylobacter jejuni enterocolitis. Infective myocarditis is most commonly due to a viral infection. Myocarditis is very rarely due to a bacterial infection with only isolated reports of myocarditis induced by Campylobacter jejuni infection. At follow-up he remains well. Myocarditis should be considered in all patients presenting with acute onset chest pain and elevated cardiac biomarkers.

Neuroleptic Malignant Syndrome

Neuroleptic Malignant Syndrome

Parvovirus B19 infection presenting as ‘bathing trunk’ erythema with pustules

A 7-year-old girl presented with acute vulval erythema and pustules, associated with a petechial eruption in her flexures and over her feet. There was a mild prodromal illness and the patient was afebrile. There were minimal symptoms associated with the rash. Skin and throat swabs were negative and blood examination showed mild neutrophilia and lymphopaenia. Parvovirus B19 IgM was detected on serology and cutaneous features resolved within 4 days. This is a further case of parvovirus B19 infection presenting as a 'bathing trunk' exanthem that has unique dermatologic features, including the presence of pustules and distant petechiae.