Cerebrospinal Fluid Exam Research Articles

Pediatric Onset Multiple Sclerosis and Obesity: Defining the Silhouette of Disease Features in Overweight Patients

Obesity has been suggested as an environmental risk factor for multiple sclerosis (MS) and may negatively effect the progression of the disease. The aim of this study is to determine any correlation between overweight/obesity and the clinical and neuroradiological features at the onset of pediatric onset multiple sclerosis (POMS). Were included patients referred to the POMS Unit of the Bambino Gesù Children’s Hospital between June 2012 and June 2021. The diagnosis of MS with an onset of less than 18 years was required. For all included subjects, we considered for the analysis the following data at the onset of symptoms: general data (age, sex, functional system compromised by neurological signs, weight and height), brain and spinal magnetic resonance imaging (MRI), cerebrospinal fluid exams. We identified 55 pediatric cases of POMS and divided them into two groups according to the body mass index (BMI): 60% were healthy weight (HW) and 40% were overweight/obese (OW/O). OW/O patients experienced a two-year age difference in disease onset compared to the HW patients (12.7 ± 3.8 years vs. 14.6 ± 4.1 years; p < 0.05). Onset of polyfocal symptoms was seen more frequently in OW/O patients than in HW (72.7% vs. 21.2%; p < 0.05). The pyramidal functions were involved more frequently in the OW/O group than in the HW group (50% vs. 25%; p < 0.005). Black holes were detected more frequently in OW/O patients in onset MRI scans compared to the HW group (50% vs. 15.5%; p < 0.05). Our findings suggest that being overweight/obese affects the risk of developing MS at an earlier age and is associated with an unfavorable clinical–radiological features at onset. Weight control can be considered as a preventive/therapeutic treatment.

Neurological Wilson Disease in a young brazilian adult: a case report

We report a rare case of Wilson Disease with neurologic features in a 31-years-old man. This disease consists of a disturbance of copper metabolism secondary to a mutation in the gene responsible for encoding the tissue transporter and the enzyme that incorporates the excess element into bile, generating toxic accumulation in the liver, cornea, and central nervous system. According to his wife, the patient had been undergoing treatment for an unspecified mood disorder. The clinical picture was characterized by depressive mood, anhedonia, and anxiety and for that, he was using Fluoxetine 40mg daily with good clinical response. He had his first seizure episode on December 3, 2021. He progressed with dysarthria, ataxic gait, dystonia of the right-hand flexor muscles, and intermittent urinary incontinence. Marked worsening was observed after diagnosis of COVID19 on February, 2022. At the clinical evaluation on March 24th, the presence of risorius muscle dystonia (risus sardonicus), resting tremor, and Kayser Fleischer rings at slit-lamp examination was also noted. Cerebrospinal fluid exam without abnormalities. Imaging workup revealed signaled alteration in bilateral putamen, midbrain, and pons. Laboratory tests revealed mild impairment of liver function and abdominal ultrasound with no evident abnormalities. Specific tests confirmed the diagnosis (serum copper and 24-hours urine copper levels elevated and reduced serum ceruloplasmin). This case report represents the importance of a detailed neurological clinical evaluation and association of findings with imaging and laboratory workup. It is a rare disease whose epidemiology in Brazil lacks data and complementary tests have reduced specificity. Early diagnosis and treatment have an impact on the neurological prognosis.

Emerging Monkeypox virus and neuroinflammatory disorders

Alarming situationMonkeypox is a zoonosis caused by a double-stranded DNA virus. The virus was isolated in monkeys in 1958. The first human case was detected in Africa in 1970. It is endemic in western and central Africa. The infection has worried public health authorities around the world since May 2022 with the emergence of thousands of cases in non-African countries. ObjectiveWe discuss the neurological manifestations associated with monkeypox infection. Rare and Severe ComplicationsAlthough in the current outbreak, the disease appears to be self-limiting, with predominance of focal skin lesions, complications may occur, mainly in children and immunosuppressed patients. Neurological manifestations such as encephalitis, convulsion, dizziness, pain, fatigue, visual alteration, photophobia, headache and myalgia were previously reported. Encephalitis may be due to viral invasion of the central nervous system or an immune-mediated process. In both situations, rapid recognition is extremely important with the investigation of the cerebrospinal fluid exam, which can demonstrate the local inflammatory reaction, specific IgM and, possibly viral detection, in addition to the imaging study. ConclusionsWe emphasize that health professionals should be alert to the emergence of neurological disorders associated with monkeypox infection in order to avoid sequelae and better characterize the current disease.

Infant Botulism: Rare but Very Dangerous Event: A Case Report

We report a case of infant botulism admitted to the Children’s Hospital “Giovanni XXIII”, Bari, Italy. After a week of constipation, hypotonia, lethargy, ptosis, reduction of suction and cry, a 2-month-old infant male, the first kid of unrelated parents was taken to the closest hospital, after being born normotrophic, at term, without a prenatal, perinatal, or postnatal medical history or neurodevelopmental delay. The patient was referred to the pediatric center for an undiagnosed progressive worsening of awareness and he was intubated for bradypnea and desaturation. The toxicologic panel, cerebrospinal fluid exam, radiological imaging, and laboratory results were negative. Only after neurological instrumental analysis, we found a normal EEG but a positive EMG that is associated with the history of raw honey intake (revealed only later by his mother). We were allowed to define the hypothesis of infant botulism earlier than the confirmation of the standard mouse bioassay. So, as a result, Botulism Immune Globulin-Intravenous IgG over 3 hours in a single recommended dose of 0.1 mL/kg/min was injected. The infant showed a gradual improvement and after 10 days he was extubated. The Preterm Oral Feeding Readiness Scale showed an improvement through the rehabilitation program with physiotherapy and parents’ stimuli. After one month he was discharged. Frequently, infant botulism is not the first hypothesis but it is the result of a strict differentiation from other diseases characterized by hypotonia such as sepsis, infectious, genetic, autoimmune, or metabolic diseases through the use of history, and laboratory tests and radiological imaging. At first, toxin detection can be useful for early diagnosis. In the later stages, the neurological instrumental support can help the clinician to elucidate the cause of muscle weakness. In fact, the EEG and the EMG could be positive when toxins are unlikely to be detectable in the serum and other data are negative. A minimum of one arm and one leg should be examined for motor and sensory nerve conduction velocity along with two distal muscles for 2-Hz nerve stimulation and a needle EMG with an adequate sample. We suggest that the neurological instrumental support can help the clinician to elucidate the cause of muscle weakness, in particular in the later stages. Honey shouldn’t be provided to infants under one-year-old children because the majority of instances still have a good history of exposure to it.

Current evidence of neurological features, diagnosis, and neuropathogenesis associated with COVID-19.

Recent reports indicate that besides respiratory and systemic symptoms among coronavirus disease (COVID-19) patients, the disease has a wide spectrum of neurological manifestations (encephalitis, meningitis, myelitis, acute disseminated encephalomyelitis, metabolic and acute hemorrhagic necrotizing encephalopathy, cerebrovascular diseases, Guillain-Barré syndrome, polyneuritis cranialis, dysautonomia, and myopathies). The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can spread from the respiratory system to the central nervous system, using transneuronal and hematogenous mechanisms. Although not every COVID-19 patient will test positive for the virus in the cerebrospinal fluid exam, the appearance of neurological symptoms associated with SARS-CoV-2 infection reveals the importance of understanding the neurologic manifestations and capacity for neural invasion associated with the pathogen. These aspects are relevant for correct diagnosis and treatment, and for the potential development of vaccines. This review highlights the latest evidence of SARS-CoV-2 infection with a focus on neurological involvement and potential neuropathogenesis mechanisms.

Cerebrospinal Fluid Analysis in Dogs and Cats with Neurological Diseases

Background:Cerebrospinal fluid (CSF) analysis is of great importance for evaluation of patients with central nervous system problems, because it helps to confirm or exclude many diseases when evaluated together with other relevant clinical and ancillary laboratory tests. As there are few studies in Brazil describing results of CSF analysis in dogs and cats, the objective of the present study was to evaluate results of CSF analysis in a period of ten years, grouping the changes observed, mainly total and differential cell count and total protein concentration, according to the following etiological categories of diseases: inflammatory, degenerative, traumatic, neoplastic and vascular disorders.Materials, Methods &Results:Medical records of dogs and cats with neurological diseases that had CSF collected and analyzed at a Veterinary Teaching Hospital between 2008 and 2017 were retrospectively reviewed. Patient data included breed, sex, body weight, age at presentation, findings of clinical and neurological examination, results of CSF analysis, diagnostic imaging and other laboratory tests results including PCR and serologies for infectious diseases. A total of 245 CSF exams were studied (240 dogs and five cats). The established normal range for protein concentration was less than 25 mg/dL for cisternal collection and less than 45 mg/dL for lumbar puncture. Total nucleated cell count was considered normal when less than 5 cells/µL, with a predominance of mononuclear cells. Both pleocytosis and increased concentration of the protein level were classified as discrete, moderate and marked, and the pleocytosis was further classified as mononuclear, neutrophilic and mixed cell pleocytosis. The information obtained was analyzed in relation to the neurological syndromes and etiological categories of neurological diseases. The most frequent syndrome was thoracolumbar and the less frequent was cerebellar. Regarding the etiological categories, the most frequent in decreasing order were inflammatory, infectious, degenerative, neoplastic, traumatic, vascular and episodic. CSF examination was abnormal in 72% of cases. In viral infectious diseases, there was predominantly mononuclear pleocytosis with a slight increase of protein, whereas in dogs with presumptive diagnosis of meningoencephalitis of unknown origin (MUO), marked mononuclear and mixed pleocytosis predominated with moderate to marked protein increase. In degenerative diseases, however, the absence of pleocytosis or mild pleocytosis, with normal to slightly increased protein was most observed. In neoplastic diseases there was a high frequency of mild to moderate pleocytosis, with and without albuminocytological dissociation, while in spinal trauma there was mainly mononuclear pleocytosis. A slight increase in protein was observed mainly in infectious, degenerative, neoplastic and traumatic diseases, while moderate to marked increase was more observed in cases of presumptive diagnosis of MUO. Albuminocytological dissociation was observed in half of the cases of neoplasia and less frequently in degenerative, infectious and traumatic diseases.Discussion: The exam was altered in a considerable number of patientsand provided important information even when normal. The diseases with more abnormalities were inflammatory/infectious and neoplastic diseases. When the exam was normal, the most frequent condition was degenerative diseases. Although the changes were not specific for each class of neurological disease, there were certain trends regarding pleocytosis type and protein increase in some of them. Based on the results of this retrospective study, result of CSF analysis, when interpreted along with signalment, etiological categories of diseases, neurological syndromes, and results of other complementary tests, provided support for the diagnosis of various neurological diseases.

Spontaneous intracranial hypotension with endolymphatic hydrops: A case report

Spontaneous intracranial hypotension may be defined as a postural headache syndrome without preceding major head trauma or dural puncture, associated with low cerebrospinal fluid volumes and opening pressure. Orthostatic headache is a cardinal clinical manifestation, associated symptoms may include neck stiffness, nausea, diplopia, vertigo, tinnitus and deafness in spontaneous intracranial hypotension. We describe a woman presented with a 1 week history of headache who was diagnosed with endolymphatic hydrops after cerebrospinal fluid analysis. A 40 years old woman presented with a 1 week history of headache. The pain was described as generalized non-throbbing and complain a mild febrile sensation. She admitted a local hospital but her symptoms were continued. On admission, she had severe orthostatic headache, nausea, vomiting and both ear fullness, tinnitus. No photophobia, phonophobia, and other autonomic dysfunction were exist. She had never been previous head or back trauma and cerebrospinal fluid tapping history. No abnormality in laboratory result. cerebrospinal fluid exam showed 4cmH2O pressure, RBC 780, WBC 0, glucose 39 (serum 83), protein 95. Brain MRI showed diffuse prominent dural enhancement by gadolinium. Pure tone audiogram: decreased hearing in low tone. It suggested endolymphatic hydrops. She treated by hydration and symptomatic treatment and symptoms were improved. In conclusion, a compensatory expansion of the endolymphatic compartment would induce endolymphatic hydrops and in the result, it causes low tone hearing loss. Because spontaneous intracranial hypotension may cause endolymphatic hydrops, it is highly probable that audiometry is necessary to the orthostatic hypotension patient with ear fullness.

Epstein-Barr virus in the cerebrospinal fluid of HIV-positive patients. Observational cross-sectional study

Different viruses are detected in the cerebrospinal fluid (CSF) of HIV-positive patients, with controversial implications in central nervous system (CNS) impairment. Objectives: to evaluate the presence, frequency and associations of Epstein-Barr virus (EB) in the CSF in HIV-positive patients. We retrospectively analyzed CSF samples from HIV-positive adult patients (≥18 years old), with or without CNS impairment, collected between Oct 2011 and Oct 2012 in a Romanian tertiary infectious diseases hospital. We performed a multiplex PCR coupled with electrospray ionization – time-of-flight mass spectrometry (Abbott Molecular) which can simultaneously detect: herpesviruses (1-5 and 8), polyomaviruses, enteroviruses, adenoviruses and parvoviruses. The patients were characterized based on the immunological and virological HIV status, neurological findings (including neuroimagery and CSF exam) and comorbidities. A number of 55 patients were analyzed, with a mean age of 33.4 years (31.5 median) and a male:female ratio of 1.9:1. The CD4 count had a mean of 32 (75 median and IQR=225). The most frequently detected virus was EB in 20/55 cases. The EB-positive subgroup had a similar mean age of 33.5 years (median of 31.0) but a different male:female ratio, of 1.2:1. The CD4 count had a mean of 105.7 (59.5 median and IQR=156). The following analyses refer to the EB-positive group: 17/20 patients had neurologic impairment. Imagery was performed in 15 cases and was normal in 5. CSF cellularity had a median of 2/cmm, IQR=10, CSF-glucose a median of 48.0 mg/dL, IQR=34 and CSF-protein a median of 55.5mg/dL, IQR=49.5. In 8/20 cases EB was found as singular agent in the CSF and in 12/20 it was associated with other microorganisms: other herpesviruses (3 cases), JC virus (4 cases), Mycobacterium tuberculosis (2 cases), Cryptococcus neoformans (2 cases) and Toxoplasma gondii (one case). The CSF-HIV viral load was available in 12/20 cases, being detectable in 10 cases. Regarding the neurological events (totalizing the neurological signs/symptoms, CSF exam and imagery), EB was probably causal in 4/20 cases, possibly causal in another 4/20 cases and was a bystander in 12/20 (3 cases with no impairment and 9 cases in which the impairments were strongly attributable to another germ). EB is the most frequent agent found in the CSF (40% of HIV-positive cases), mainly in women. It can be mono-detected but it especially appears in multiple associations. In more than half of the cases EB acts as an innocent bystander.

Rotigotine for Apathy in Limbic Autoimmune Encephalitis

Rotigotine for Apathy in Limbic Autoimmune Encephalitis

Three Cases of Neoplastic Meningitis Initially Diagnosed with Infectious Meningitis in Emergency Department

Neoplastic meningitis (NM) is diagnosed by the presence of malignant cells in the cerebrospinal fluid (CSF). We report 3 patients with NM, who were misdiagnosed with infectious meningitis in emergency department (ED). Case 1. A 68-year-old man visited our ED with a 3-month history of headache. With MRI and CSF study, he was diagnosed with tuberculous meningitis. After 20 days, repeated CSF cytology showed malignant cells. His diagnosis was lung cancer with NM. Case 2. A 57-year-old man visited regional hospital ED with a 3-week history of headache and diplopia. Brain MRI was not contributory. With CSF examination, his diagnosis was aseptic meningitis. With worsening headache, he was referred to our ED. Repeated CSF showed malignant cells. His diagnosis was stomach cancer with NM. Case 3. A 75-year-old man visited a regional hospital with headache lasting for 4 months. His diagnosis was sinusitis. Persistent symptom brought him back, and he developed recurrent generalized seizures. Brain MRI showed diffuse leptomeningeal enhancement suggesting meningitis, and he was transferred to our ED. CSF exam showed malignant cells. His diagnosis was NM with unknown primary focus. When evaluating the patients with headache in ED, NM should be kept in mind as a differential diagnosis of meningitis.

Early Detection of BCR-ABL Fusion Gene of Cerebrospinal Fluid (CSF) by RT-PCR in Relapsed Acute Lymphoblastic Leukemia with Philadelphia Chromosome

As polymerase chain reaction (PCR) is increasingly applied in clinical medicine, early detection and more accurate diagnosis is possible. Using molecular methods with cerebrospinal fluid (CSF) samples in addition to existing cytological methods is of value even if only occult malignant cells are present. We describe a case of central nervous system (CNS) leukemia in a patient with Philadelphia chromosome–positive acute lymphoblastic leukemia confirmed by reverse transcription PCR (RT-PCR) in a CSF specimen from a patient who was treated with chemotherapy (Hyper CVAD protocol, including cyclophosphamide, vincristine, adriamycin, prednisolone, and intrathecal methotrexate). Study of her CSF identified atypical lymphocytes. To ensure that the diagnosis was correct, we conducted a CSF exam using RT-PCR and confirmed CNS relapse by identifying the BCR-ABL gene. After remission, a CNS relapse occurred in the form of optic nerve involvement. Despite treatment, the patient died of leukemia progression and multiple organ failure with sepsis. We discuss the diagnostic role of RT-PCR with CSF samples for early and accurate detection of CNS relapse and review the relevant literature on this subject.

Importancia de las imágenes y el diagnóstico etiológico en el paciente inmunocomprometido con afección del sistema nervioso central: Tercera parte

A twenty four year-old male patient with a history of morbid obesity and acute lymphocytic leukemia diagnosed in 2003, underwent an autologous bone marrow transplantation the same year. He had two relapses of leukemia on 2003 and 2007. On January 2009, he underwent a double cord bone marrow transplantation with myeloablative conditioning and craneospinal radiotherapy. The patient received prophylaxis with aciclovir, cotrimoxazole and fluconazole. The latter was changed afterwards to posaconazole. On day 16 post-transplantation, fever and meningeal signs appeared. The cerebrospinal fluid exam revealed pleocytosis with polymorphonuclear predominance. Empirical therapy was started with meropenem. Due to neurological impairment, at day 33, a brain magnetic resonance imaging (MRI) was performed, showing multiple hypodense supra and infratentorial nodules with peripheral edema. Biopsy, universal PCR for fungi and a new cerebrospinal fluid analysis were performed and amphotericin B was added showing a favorable response. He was discharged with itraconazole, as the universal PCR of brain tissue revealed Penicillium spp. This is the third report presented in this journal that stresses the importance of early neuroimaging, especially MRI to certify the involvement of the central nervous system in immunocompromised patients.

Diagnosis of Alzheimer's disease in Brazil: Supplementary exams.

This article presents a review of the recommendations on supplementary exams employed for the clinical diagnosis of Alzheimer’s disease (AD) in Brazil published in 2005. A systematic assessment of the consensus reached in other countries, and of articles on AD diagnosis in Brazil available on the PUBMED and LILACS medical databases, was carried out. Recommended laboratory exams included complete blood count, serum creatinine, thyroid stimulating hormone (TSH), albumin, hepatic enzymes, Vitamin B12, folic acid, calcium, serological reactions for syphilis and serology for HIV in patients aged younger than 60 years with atypical clinical signs or suggestive symptoms. Structural neuroimaging, computed tomography or – preferably – magnetic resonance exams, are indicated for diagnostic investigation of dementia syndrome to rule out secondary etiologies. Functional neuroimaging exams (SPECT and PET), when available, increase diagnostic reliability and assist in the differential diagnosis of other types of dementia. The cerebrospinal fluid exam is indicated in cases of pre-senile onset dementia with atypical clinical presentation or course, for communicant hydrocephaly, and suspected inflammatory, infectious or prion disease of the central nervous system. Routine electroencephalograms aid the differential diagnosis of dementia syndrome with other conditions which impair cognitive functioning. Genotyping of apolipoprotein E or other susceptibility polymorphisms is not recommended for diagnostic purposes or for assessing the risk of developing the disease. Biomarkers related to the molecular alterations in AD are largely limited to use exclusively in research protocols, but when available can contribute to improving the accuracy of diagnosis of the disease.

Central nervous system relapse in pediatric acute lymphoblastic leukemia: Should we be making the diagnosis sooner?

9567 Background: Central nervous system (CNS) disease in acute lymphoblastic leukemia (ALL) is based solely on consensus guidelines, which define involvement as the presence of at least 5 white blood cells (WBC) per μL in the cerebrospinal fluid (CSF) with lymphoblasts (CNS3) (Med Pediatr Oncol:1986;14). Relapsed disease utilizes the same definition unless there are immunohistochemical or flow cytometric markers prior to the advent of CNS3 disease. We have observed patients with multiple consecutive abnormal CSF cytology exams prior to meeting the standard definition of CNS relapse and wonder if this may be a sufficient criterion for relapsed disease. Methods: We reviewed all CSF cytology reports for ALL patients treated at our institution from 2003 through 2010. We then reviewed all cytology slides from patients with CNS relapse, comparing the pre-relapse slides to those from the relapse specimen, applying the method of Goldsby et al. (Med Pediatr Oncol:1997;29). Results: 239 patients had 3425 CSF cytology exams. Ten patients had CNS relapse, 9 of which had morphologic evidence of early CSF leukemic involvement, ranging from 7 to 28 weeks (median 13, mean 15 weeks), before meeting the standard definition for relapse. Consecutive CSF analysis with suspicious cells (WBC < 5/μL) outside induction was highly significant for the presence of relapsed CNS disease: 6 of the 10 patients with eventual CNS3 relapse had this finding, as compared to 3 of 225 patients (0.3% of all CSF examined) without CNS disease (p<0.0001 by Fisher’s Exact test; excluding 4 patients, 2 treated for CNS disease before CNS3, 2 with abnormal CSF with peripheral blasts at or after bone marrow relapse). Conclusions: Patients with CNS relapse may wait months with cells suspected of being leukemic prior to developing CNS3 disease. In our analysis, consecutive abnormal CSF exams without pleiocytosis was highly significant for relapse. With careful morphologic analysis, we suggest the diagnosis of CNS relapse can be confidently established earlier than is currently done. Continuing a failing treatment regimen in these cases increases parental and patient anxiety and could potentiate resistant disease and worse outcomes.

Pseudotumor cerebri and ciprofloxacin: a case report

IntroductionWe present a case of ciprofloxacin-associated pseudotumor cerebri in a 22-year-old African American woman. Withdrawal of ciprofloxacin in our patient resulted in complete resolution of ciprofloxacin-associated pseudotumor, as evidenced by a normal neuro-ophthalmic examination and a cerebrospinal fluid opening pressure of 140 mmH20.Case presentationA 22-year-old African American woman presented with a headache of two weeks duration, visual blurring and horizontal diplopia after starting ciprofloxacin for pyelonephritis. An ophthalmic examination revealed that she had left eye esotropia, and a picture of the fundus demonstrated bilateral disc swelling without spontaneous venous pulsations. Magnetic resonance imaging of the brain and a magnetic resonance venogram were normal. A diagnostic lumbar puncture demonstrated an elevated opening pressure of 380mmH2O in a supine position. Laboratory examinations, including a cerebrospinal fluid exam, were unremarkable.Conclusionciprofloxacin-associated pseudotumor can cause chronic disabling headache and visual complications. Therapy is sub-optimal, often symptomatic, insufficient and complicated by side effects. When ciprofloxacin-associated pseudotumor presents in an atypical population, an inciting agent must be suspected because prompt withdrawal of the agent may lead to complete resolution of symptoms and prevent recurrence of similar episodes.

M2015 Functional Dyspepsia and Sleep

prospectively identified CIPO patients. Methods: 25 CIPO patients (10 F, age range: 16-85 yrs), diagnosed between 2006 and 2009 according to defined criteria (Stanghellini et al., Gut, 1987), entered the study. Each patient underwent a formal neurological assessment, electromyography and sympathetic skin response. Based on the neurological examination and neurophysiological tests, CIPO patients were divided into three groups: 1) polyneuropathy; 2) suspected mitochondrial encephalomyopathy; and 3) idiopathic CIPO. Group 1 and 2 were examined by skeletal muscle or skin biopsy, microneurography, MR spectroscopy, genetic tests as well as serological and cerebrospinal fluid exams, to define the origin of their neurological impairment. Results: A number of 8/25 (32%) CIPO showed neurological impairment: 5 patients had mitochondrial encephalomyopathies and 3 peripheral small fiber (including autonomic) neuropathy. Of the 5 encephalomyopathies, 4 had mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) with mutations in TP/ECGF1 gene and 1 had myoclonic epilepsy and ragged red fiber disease (MERRF) phenotype carrying the 3243A>G mtDNA MELAS mutation. Notably, these patients came to medical observation because of prominent and severe gastrointestinal symptoms present at the onset of their disease. Muscle biopsies showed COX negative fibers in the MNGIE and MERRF patients, whereas theMERFF patient also had red-ragged fibers. Increased SDH staining andmyopathic features were seen in all biopsies. mtDNA analysis revealed a combination of multiple deletions and depletion in the MNGIE and MERFF patients. Ultrastructural analysis showed intramitochondral paracrystalline inclusions. Of the 3 patients with small fibers polyneuropathy, 1 had chronic inflammatory demyelinating polyneuropathy, whereas 2 had an idiopathic disease. Notably, the first patient of this group improved dramatically with a high dose course of i.v. Ig therapy. Conclusions: Accurate evaluation and tests unravelled a subgroup of CIPOpatients with a neurological origin.Mitochondrial diseases and peripheral neuropathy can both contribute to severe gut dysmotility. Neurological identification is crucial for an appropriate management of these complicated cases.

M2017 Assessment of Hypercoagulability in Drug Refractory Gastroparesis Patients Undergoing Permanent Gastric Electrostimulation

prospectively identified CIPO patients. Methods: 25 CIPO patients (10 F, age range: 16-85 yrs), diagnosed between 2006 and 2009 according to defined criteria (Stanghellini et al., Gut, 1987), entered the study. Each patient underwent a formal neurological assessment, electromyography and sympathetic skin response. Based on the neurological examination and neurophysiological tests, CIPO patients were divided into three groups: 1) polyneuropathy; 2) suspected mitochondrial encephalomyopathy; and 3) idiopathic CIPO. Group 1 and 2 were examined by skeletal muscle or skin biopsy, microneurography, MR spectroscopy, genetic tests as well as serological and cerebrospinal fluid exams, to define the origin of their neurological impairment. Results: A number of 8/25 (32%) CIPO showed neurological impairment: 5 patients had mitochondrial encephalomyopathies and 3 peripheral small fiber (including autonomic) neuropathy. Of the 5 encephalomyopathies, 4 had mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) with mutations in TP/ECGF1 gene and 1 had myoclonic epilepsy and ragged red fiber disease (MERRF) phenotype carrying the 3243A>G mtDNA MELAS mutation. Notably, these patients came to medical observation because of prominent and severe gastrointestinal symptoms present at the onset of their disease. Muscle biopsies showed COX negative fibers in the MNGIE and MERRF patients, whereas theMERFF patient also had red-ragged fibers. Increased SDH staining andmyopathic features were seen in all biopsies. mtDNA analysis revealed a combination of multiple deletions and depletion in the MNGIE and MERFF patients. Ultrastructural analysis showed intramitochondral paracrystalline inclusions. Of the 3 patients with small fibers polyneuropathy, 1 had chronic inflammatory demyelinating polyneuropathy, whereas 2 had an idiopathic disease. Notably, the first patient of this group improved dramatically with a high dose course of i.v. Ig therapy. Conclusions: Accurate evaluation and tests unravelled a subgroup of CIPOpatients with a neurological origin.Mitochondrial diseases and peripheral neuropathy can both contribute to severe gut dysmotility. Neurological identification is crucial for an appropriate management of these complicated cases.

Pilocytic astrocytoma of the spinal cord in an adult

Case presentationA 42-year-old man presented with a 9-month history ofprogressive numbness and paresthesias involving theupper limbs. His symptoms started at the fourth and fifthdigits of both arms, and ascended to involve the elbows.Within several weeks, the lower limbs became involvedwith the numbness and pain starting at the toes andprogressing up to mid thorax. He had no bowel or bladderinvolvement. His examination showed no stigmata ofsystemic disease. He had minimal weakness at hip flex-ion, upper motor neuron signs in all limbs, decreasedsensation in C8 distribution bilaterally, and a sensorylevel at T4 sparing proprioception. Magnetic resonanceimaging (MRI) of the spinal cord 6 and 9 months(September 2006, December 2006) after symptom onsetrevealed T2 prolongation and cord edema (Fig. 1a, c)with an 8 mm enhancing intramedullary lesion at the C5-6 (Fig. 1b, d). The possibility of demyelinating diseasewas considered. Thoracic and brain MRI where unre-markable. Further workup included cerebrospinal fluid(CSF) which revealed leukocytosis of 13 with 88% lym-phocytic predominance, protein of 310 mg/dl, normalglucose and two oligoclonal bands not present in a cor-responding serum sample. The patient continued todevelop progressive neurological deficits that did notrespond to treatment with 5 days of 1 g intravenousMethylprednisolone. Repeated CSF exam showed persis-tence of protein elevation (289 mg/dl), normalization ofleukocytosis and absence of oligoclonal bands. Bothexaminations showed normal cytology. Anti nuclearantibodies (ANA), Lyme serology, angiotensin convertingenzyme (ACE), HTLV-1 serology, B12 level, anti-neutr-ophilic cytoplasmic antibodies (ANCA) were all normal.CT scans of the chest, abdomen and pelvis excludedoccult malignancy and lymphadenopathy. Magnetic reso-nance angiography (MRA) and spinal angiogram showednormal cerebral and spinal vasculature. Repeated spineMRI (February 2007, July 2007) showed mildly increas-ing edema at the site of cervical spinal cord lesion, butstable lesion size and unchanged enhancement pattern.Differential diagnosis included a neoplastic process due tothe persistent duration of enhancement, the elevated pro-tein in the CSF, and absence of clinical or radiographicimprovement after treatment with intravenous steroids.As the etiology of the lesion was not clear preopera-tively, i.e. intramedullary neoplasm or ischemia fromstenosis, the patient underwent C4-T1 decompression,posterior spinal fusion, posterior laminectomy, and intra-dural subtotal mass resection. Intraoperatively the surfaceof the cord and the vasculature looked normal. The cord

The 59th Annual Meeting of the American Academy of Neurology, Boston, Massachusetts April 28-May 5, 2007

The 59th Annual Meeting of the American Academy of Neurology, Boston, Massachusetts April 28-May 5, 2007

Anterior lumbosacral polyradiculopathy after intrathecal administration of methotrexate

Transient paraparesis has been reported with intrathecal chemotherapy agents and the most common cause is an incomplete inflammatory myelopathy. We report a case of a 30-year-old man diagnosed with acute lymphoblastic leukaemia who developed subacute anterior lumbosacral polyradiculopathy following intrathecal methotrexate, an unusual complication of intrathecal chemotherapy in adults. Spinal magnetic resonance discarded myelopathy. Cerebrospinal fluid exam showed elevation of protein, mononuclear pleocytosis and immunoglobulin synthesis. Electrodiagnostic study showed alterations of sensory and motor conductions only in lower limbs, consistent with multilevel radiculopathy. Differential diagnosis included toxic and neoplastic polyradiculopathy, and axonal variant of acute inflammatory demyelinating polyradiculoneuropathy. The authors review possible pathogenic mechanisms and propose several therapeutic and preventive options.