[Legionnaires' disease with pronounced cerebellar involvement: case report and literature review].

Objective: To summarize the clinical course, neuroimaging and cerebrospinal fluid (CSF) analyses of cerebellar dysfunction in Legionnaires' disease. Methods: A case of Legionnaires' disease with pronounced cerebellar involvement was reported. The related literatures published up to February 2019 were reviewed with "Legionella, legionellosis, legionnaires' disease, cerebellum, cerebellar" as the keywords in CNKI, Wanfang and PubMed databases. Results: A 69-year-old man complained of anorexia and diarrhea for several days. He was subsequently admitted to the hospital after he had fever, ataxia, dysarthria and involuntary tremor. Chest CT revealed right lower lobe pneumonia. Routine urinalysis showed hematuria and proteinuria. Serum alanine transaminase was 52 U/L, creatinine 137 µmol/L, sodium 128 mmol/L, and creatine kinase 6 893 U/L. Cranial CT was normal. Analysis of CSF showed mildly elevated total protein. Legionella colonies isolated from bronchoalveolar lavage fluid was positive by PCR. After initial treatment with moxifloxacin and azithromycin for 7 days, the fever and neurological symptoms persisted. Corticosteroid therapy was administered for 3 days, the fever resolved, whereas the neurological symptoms improved gradually and slowly by 4 weeks of antibiotic therapy. Finally, successive serological test confirmed Legionella pneumophila serogroups 6 and 7 by indirect immunofluorescence. Twenty-one literatures with 23 cases were reviewed, and plus our case, there were a total of 24 cases for analysis. There were 16 males and 8 females, aged from 22 to 71 years. Ataxia and dysarthria were the cerebellar symptoms most frequently reported, occurring in 22 and 18 cases, respectively. All patients had various central and peripheral neuropathies during their illness. Neuroimaging and analysis of CSF was reported in 21 cases. There were no abnormalities in 18 cases of cranial imaging, 1 case with slight hydrocephalus on cranial CT, and 3 cases with hyperintensity in the splenium of corpus callosum on cranial MRI. Eighteen cases of CSF analyses were normal, whereas 1 case with elevated lymphocytes and 3 cases with elevated proteins. Nine cases were eventually identified as Legionella pneumophila serotype 1 by urinary antigen detection, 1 case as Legionella pneumophila serogroups 6 and 7, while the remaining 14 were unknown serotype. Long-term neurologic follow-up showed that 3 cases recovered completely in the first week, while 19 cases improved slowly in the following 3 weeks, and 13 cases had persistent deficits of gait or speech after 3 months. Conclusions: Legionellosis with cerebellar insufficiency is rare. It may be misdiagnosed in the onset of illness. After treatment, there is a trend of slow recovery and neurological symptoms may persist in long-term follow-up.

Cerebral folate deficiency in adults: A heterogeneous potentially treatable condition.

OBJECTIVE: To describe the phenotype and the response to folinic acid supplementation of cerebral folate deficiency (CFD) in adults, a disorder diagnosed on low 5-methyltetrahydro-folate (5MTHF) in cerebrospinal fluid (CSF), which can correspond to a inherited disorder of folate metabolism (IDFM) or to a metabolic consequence of various neurological diseases. METHODS: We conducted a retrospective study on 224 adult patients with neurological symptoms who had a 5MTHF CSF dosage, collecting their neurologic and neuroimaging data. RESULTS: 69 patients had CFD (CSF 5MTHF level < 41 nmol/L), 25 of them had severe CFD (sCFD; ≤25 nmol/L) with adult onset neurological symptoms in 41%. 56% of sCFD patients had an underlying identified neurologic disorder, mainly mitochondrial diseases, hepatic encephalopathy and primary brain calcifications (no identified IDFM), the others were classified as undiagnosed. sCFD patients presented most frequently pyramidal syndrome (75%), movement disorders (56%), cerebellar syndrome (50%) and intellectual disability (46%). MRI findings mostly showed white matter abnormalities (WMA; 32%) and calcifications (12%), and were normal in 23%. The clinico-radiological phenotype of sCFD patients was not clearly different from non CFD patients in terms of manifestations frequency. However, their neurological picture was more complex with a higher number of combined neurological symptoms (4.7±1.6 vs 3.4±1.7, p = .01). In Magnetic Resonance Spectroscopy (MRS), Choline/Creatine (Cho/Cr) ratio was lower in sCFD patients (n = 7) compared to non-CFD patients (n = 73) (p = .005), with good sensitivity (71%) and excellent specificity (92%). Among twenty-one CFD patients treated with folinic acid, nine had a sustained improvement, all with sCFD but one (50% of sCFD patients improved). In two undiagnosed patients with extremely low 5MTHF CSF values, MRI WMA and low Cho/Cr ratios, folinic acid treatment leaded to a dramatic clinical and radiological improvement. CONCLUSION: CSF 5MTHF dosage should be considered in patients with mitochondrial diseases, primary brain calcifications and unexplained complex neurological disorders especially if associated with WMA, since folinic acid supplementation in patients with sCFD is frequently efficient.

Acute cerebellitis in adults: a case report and review of the literature.

BACKGROUND: Acute cerebellitis is a rare disease with the majority of cases described in children. Little is known about the clinical characteristics and outcome in adults. CASE PRESENTATION: A 37-year-old Caucasian woman presented with headache, nausea, and photophobia, and was diagnosed as having a migraine attack. Two days later, she subsequently returned with aggravated headache, dysarthria and horizontal nystagmus. Magnetic resonance imaging (MRI) showed a swollen cerebellum and hydrocephalus and the patient was diagnosed with acute cerebellitis. Cerebrospinal fluid (CSF) examination showed an elevated leukocyte count and protein. Blood serology showed the presence of immunoglobulin M and immunoglobulin G for both Epstein-Barr virus and cytomegalovirus. The patient was treated with dexamethasone and discharged to a rehabilitation center, where she fully recovered. We searched the literature for adult cases of acute cerebellitis. Including our patient, we identified 35 patients with a median age of 36 years. The etiology was unknown in 34% of cases. The most common clinical presentation consisted of headache, nausea/vomiting and ataxia. Six patients presented with only headache and nausea and subsequently returned with cerebellar signs. In 9 cases, the cerebellitis was complicated by hydrocephalus. Half of the patients ended up with neurological sequelae, while follow-up MRI was abnormal in 71%. CONCLUSION: Acute cerebellitis in adults is a rare disorder which mainly presents with headache, nausea/vomiting and ataxia. To diagnose cerebellitis, imaging of the brain (preferably MRI) is required and CSF examination may be necessary to narrow the differential diagnosis. The treatment depends on the widely diverse etiology, and treatment with steroids is recommended in the case of cerebellar oedema and hydrocephalus. Neurosurgical intervention may be necessary to prevent brain herniation.

Cerebellar disease associated with anti-glutamic acid decarboxylase antibodies: review.

Several neurological syndromes have been recognized associated to GAD antibodies. Among those disorders, cerebellar ataxia (CA) is one of the most common, along with stiff-person syndrome. Patients with GAD associated CA present with a progressive pancerebellar syndrome, with a subacute or chronic evolution, along with other neurological manifestations such as stiffness, oculomotor dysfunction, epilepsy, and cognitive dysfunction. These symptoms may be preceded by the so-called "brainstem attacks", where manifestations consistent with transient dysfunction of the brainstem may be observed. These patients frequently have extra-neurologic autoimmune manifestations such as diabetes mellitus type 1, polyendocrine autoimmune syndrome, pernicious anemia, vitiligo, etc. A proportion of patients may present with an underlying neoplasia, but the course is less aggressive than in those patients with classical paraneoplastic CA with onconeural antibodies. The diagnosis is based on the present of high serum and CSF titers of GAD antibodies, with intrathecal production of such antibodies. Treatment is aimed to decrease the immunological response with intravenous immunoglobulin, steroids, rituximab and oral immunosuppressive drugs. A subacute presentation and rapid initiation of immunotherapy seem to be the predictors of a favorable clinical response.

Total folate and 5-methyltetrahydrofolate in the cerebrospinal fluid of children: correlation and reference values.

BACKGROUND: Cerebral folate deficiency (CFD) may be underdiagnosed, as it manifests with various non-specific neurological symptoms. The diagnosis of CFD requires a determination of 5-methyltetrahydrofolate (5MTHF) in the cerebrospinal fluid (CSF), which is available in a limited number of specialized laboratories. In clinical biochemistry laboratories, total folate (TF) determination in serum or plasma is routinely performed by automated analyzers. The aim of this study is to determine whether the automated assay of CSF TF is a helpful screening tool for CFD. METHODS: We analyzed CSF samples collected from 73 pediatric patients. We measured CSF TF, serum TF, and CSF 5MTHF in 73, 70, and 48 patients, respectively. The assay of 5MTHF was conducted by a newly developed system utilizing liquid chromatography-tandem mass spectrometry (LC-MS/MS). We investigated the correlation between TF and 5MTHF in the CSF. RESULTS: There was a strong positive correlation between CSF TF and 5MTHF (ρ=0.930, p<0.0001, n=48). Age was negatively correlated with CSF TF (ρ=-0.557, p<0.0001, n=51), serum TF (ρ=-0.457, p=0.0008, n=51), and CSF 5MTHF (ρ=-0.387, p=0.0263, n=33), but not with the CSF/serum TF ratio. CONCLUSIONS: The automated assay of CSF TF is helpful to estimate CSF 5MTHF. The CSF TF assay may have a significant impact on the early diagnosis of CFD, because clinicians have better access to it than the 5MTHF assay.

14-3-3 proteins, particularly of the epsilon isoform, are detectable in cerebrospinal fluids of cerebellar diseases in children.

BACKGROUND: Detection of 14-3-3 proteins in cerebrospinal fluid (CSF) is a powerful tool for elucidating the mechanisms of neurological disorders. There have been useful studies on 14-3-3 CSF protein detection in Creutzfeldt-Jakob disease and other neurological disorders, but none on cerebellar diseases. OBJECTIVE: To elucidate whether 14-3-3 CSF proteins are a sensitive biomarker of cerebellar disruption in children. MATERIALS AND METHODS: We examined 14-3-3 CSF proteins by immunoblotting in seven patients with cerebellar disorders: two with acute cerebellitis, two with acute cerebellar ataxia, and three with cerebellar atrophy. We also investigated 14-3-3 CSF proteins in four cases of febrile seizure and three of influenza-related encephalopathy. Isoforms of 14-3-3 proteins were also identified using isoform-specific antibodies. RESULTS: 14-3-3 proteins were detected in CSF of six patients with cerebellar disorders, the exception being one with acute cerebellar ataxia caused by viral infection. Interestingly, only the 14-3-3 ε isoform was detected in two tested patients with cerebellar involvement. Moreover, longitudinal analysis of 14-3-3 CSF proteins in one patient with infantile neuroaxonal dystrophy showed that the 14-3-3 band density proportionally decreased when the cerebellar atrophy gradually progressed. Another CSF derived from a case of febrile seizure showed no 14-3-3 proteins, whereas all those derived from influenza-related encephalopathy demonstrated 14-3-3 CSF proteins with six isoforms. CONCLUSIONS: This is the first report on 14-3-3 CSF proteins as a significant biomarker of cerebellar disruption, as well as other brain diseases. Since 14-3-3 ε is localized in the molecular layer of cerebellum, the unique detection of 14-3-3 ε may indicate cerebellar involvement in the brain.

Balanced steady-state free-precession MR imaging for measuring pulsatile motion of cerebellar tonsils during the cardiac cycle: a reliability study.

INTRODUCTION: Assessment of the motion of the cerebellar tonsils is of interest in diseases affecting the CSF flow at the foramen magnum. Cardiac-gated balanced steady-state free-precession technique, which has recently been shown to demonstrate the pulsatile motion of neural structures, appears well suited to allow direct measurement of craniocaudal translation of cerebellar tonsils during the cardiac cycle. Our aim was to assess the intra-observer and inter-observer variability in the assessment of tonsillar motion utilizing this technique. METHODS: We retrospectively identified 44 patients who had undergone MR imaging with cine TrueFISP sequence, as a part of CSF flow study. Two neuroradiologists independently assessed the images. The tonsillar pulsatility was subjectively characterized into none, minimal, and marked categories after review of the images on a cine loop. For patients with identifiable tonsillar motion, the maximal extent of translation of the inferior edge of the cerebellar tonsil was directly measured. Both readers repeated the measurements after a minimum interval of 2 weeks. Intra- and inter-observer variability was characterized by calculating the kappa statistics. RESULTS: The intra-observer agreement for subjective assessment of tonsillar pulsatility was near perfect while the inter-observer agreement was substantial. A good intra- and inter-observer correlation was also seen for the objective measurements of the tonsillar motion. A good correlation was found between the subjective categorization of the tonsillar pulsatility and the objective measurements. CONCLUSION: Steady-state balanced free-precession MR imaging technique allows for a reproducible subjective and objective assessment of tonsillar pulsatility.

Bri2-23 is a potential cerebrospinal fluid biomarker in multiple sclerosis.

To identify potential multiple sclerosis (MS)-specific biomarkers, we used a proteomic approach to screen cerebrospinal fluid (CSF) from 40 MS patients and 13 controls. We identified seven proteins (Beta-2-microglobulin, Bri2-23, Fetuin-A, Kallikrein-6, Plasminogen, Ribonuclease-1, and Transferrin) that had significantly altered levels in MS compared to controls. Clinical subgroup analysis revealed that decreased CSF levels of Bri2-23, a peptide cleaved from Bri2, were significantly associated with patients having cerebellar dysfunction and cognition impairment. Furthermore, expression levels of Bri2 were specifically decreased in the cerebellum compared to other areas of same brain in MS but not in controls, suggesting that decreased cerebellar Bri2 expression may play a role in cerebellar dysfunction. The association with cognition impairment is also of interest because Bri2 is linked to the amyloid processing pathway in the brain. CSF levels of Bri2-23 may serve as a biomarker of these functions in MS and merits further investigation.

Central system nervous tuberculosis in infants.

The lack of specific symptoms and signs in patients with tuberculous meningitis makes early diagnosis difficult. In this report, we reviewed the clinical features and laboratory findings of 6 infants with central system nervous tuberculosis during a 10-year period. One of the patients had multifocal tuberculosis. The mean time to the diagnosis was 32 +/- 13.4 days. A contact source was identified in only 2 patients. All 6 patients had abnormal cerebrospinal fluid findings, less than 500 cells/microL with lymphocytic predominance. Computerized tomography (CT) and/or magnetic resonance imaging (MRI) revealed hydrocephalus with basal enhancement in 2 patients. One patient developed pontocerebellar and pituitary tuberculomas, which were responsible for compression and diabetes insipidus, 1 year after antituberculous treatment. These localizations are very rare. On the follow-up, 3 patients had hypoacousia and only 1 had severe sequelae, despite a diagnostic delay.

Elevated B-cell activating factor BAFF, but not APRIL, correlates with CSF cerebellar autoantibodies in pediatric opsoclonus-myoclonus syndrome.

Childhood opsoclonus-myoclonus syndrome (OMS) occurs idiopathic or, in association with a neuroblastoma, as a paraneoplastic syndrome. Since autoantibodies were identified in some patients, an autoimmune pathogenesis has been suspected. While the newly discovered B-cell activating factors BAFF and APRIL are involved in systemic autoimmune diseases, their association with neuroimmunological diseases is hardly understood. We here investigated the BAFF and APRIL levels in serum and cerebrospinal fluid (CSF) of OMS patients and their correlation with surface-binding autoantibodies. BAFF and APRIL were both determined by ELISA, and autoantibodies to cerebellar granular neurons (CGN) have been investigated by flow cytometry in 17 OMS patients, 16 neuroblastoma (NB) patients, 13 controls and 11 children with inflammatory neurological diseases (IND). BAFF, but no APRIL, was elevated in the CSF of OMS children and IND children. However, in contrast to IND patients, OMS patients did not have a blood-brain-barrier disturbance, indicating that BAFF was produced intrathecally in OMS patients, but not in IND patients. CSF BAFF levels showed a correlation with CSF CGN autoantibodies (r(2)=0.58, p<0.05). These data indicate that an activated B-cell system in the cerebrospinal fluid is involved in the pathogenesis of OMS, and BAFF may be a candidate parameter for the activation of B-cell immune system.

Remote cerebellar hemorrhage: a review.

Remote cerebellar hemorrhage remains a complication rarely occurring after supratentorial surgery (<5%) and presumably even less frequent after spinal surgery. Although the pathomechanisms leading to RCH with its typical bleeding pattern are still not definitely understood, intra- or even more likely postoperative loss of larger volumes of CSF seem to be related to this complication. Prognosis significantly depends on severity of hemorrhage and patient age. Outcome in more than 50% of all cases is good with only mild remaining neurological symptoms or complete recovery, while death occurs in approximately 10-15%. Close monitoring of patients undergoing surgery that involves the risk of draining large volumes of CSF is mandatory and patients with postoperative drainage of larger amounts of fluid acquire increased attentiveness. Early detection and correct interpretation of the typical bleeding pattern might help to avoid further aggravation of symptoms. This review will address incidence, typical appearance and pathophysiological considerations, as well as risk factors, treatment options, and outcome related with RCH.

Detection of herpesvirus-6A in a case of subacute cerebellitis and myoclonic dystonia.

This is a case study of a child who developed roseola infantum first, then varicella, and was later affected by acute cerebellar syndrome, severe truncal ataxia, and myoclonic dystonia. Human herpesvirus 6 (HHV-6) A and B were detected in the cerebrospinal fluid (CSF) and peripheral blood, respectively, upon ataxia onset. The intricacy of this case suggests multifaceted conclusions ranging from the need for a multidirectional approach to neurological diseases, to confirmation of a more pronounced neurotropism of HHV-6A and a possible role of viruses in myoclonic dystonia syndrome, although this last hypothesis should be confirmed by larger studies.

Paraneoplastic antibodies detected by isoelectric focusing of cerebrospinal fluid and serum.

Patients with paraneoplastic neurological syndromes often produce intrathecal antibodies. We have employed isoelectric focusing and peroxidase-labeled anti-IgG or 35S-labeled Hu or Yo antigens to identify oligoclonal bands (OCB) representing either total IgG or Hu or Yo antibodies in serum and CSF of patients with paraneoplastic encephalomyelitis (PEM) or paraneoplastic cerebellar degeneration (PCD). OCBs representing paraneoplastic antibodies were found in all CSF, but in only three sera. Yo antibodies represented the majority of IgG bands in PCD-CSF, which may reflect a limited immune response, whereas in PEM/SN, there were numerous additonal IgG bands of unknown specificity, indicating a broader immune response in these patients.

Cerebellitis in an adult with abnormal magnetic resonance imaging findings prior to the onset of ataxia.

BACKGROUND: Brain magnetic resonance imaging (MRI) findings during acute cerebellar ataxia in cases of postinfectious cerebellitis are frequently normal. This has resulted in the use of other imaging modalities, such as single-photon emission computed tomography, to aid diagnosis. OBJECTIVE: To illustrate the chronologic occurrence of cerebellar ataxia, abnormal findings on MRI, and cerebral spinal fluid pleocytosis in an adult case of postinfectious cerebellitis. METHODS: Case report. RESULTS: A patient with a 6-week history of occipital headaches and only mild tandem gait difficulty had abnormal MRI findings that were consistent with cerebellar inflammation. As cerebellar ataxia progressed in parallel with cerebral spinal fluid pleocytosis, MRI findings indicative of cerebellar inflammation resolved, while single-photon emission computed tomography showed cerebellar hyperperfusion. Recovery of neurologic function was accompanied by clearing of the pleocytosis and residual MRI-detected cerebellar atrophy. CONCLUSION: This case demonstrates that transient abnormalities can be detected by MRI before clinical manifestations of cerebellitis appear, while hyperperfusion detected by single-photon emission computed tomography is prolonged.

Acute cerebellitis caused by herpes simplex virus type 1.

Cerebellar disorders due to herpes simplex virus (HSV) infection are rare and always associated with herpes simplex encephalitis. We report 2 cases of severe primary acute cerebellitis caused by HSV type 1 that were identified by nested polymerase chain reaction performed on cerebrospinal fluid samples.

[Infection due to Mycoplasma pneumoniae: three cases with neurological complications]. / Infección por Myoplasma Pneumoniae: tres casos con complicaciones neurológicas.

INTRODUCTION: Mycoplasma pneumoniae infection has been associated with severe central nervous system diseases. The pathogenesis of these disorders is unknown and the treatment uncertain. CASE REPORTS: The authors present three cases of central nervous system diseases: acute transverse myelitis, cerebellitis and encephalomyelitis associated with M. pneumoniae infection. CONCLUSIONS: M. pneumoniae infection should be considered in all cases of severe acute central nervous system symptomatology.

Mumps with cerebellar encephalitis.

A 30 years male patient, having typical symptoms of mumps, presented with acute cerebellar ataxia two days after the onset of parotid enlargement. The neurological symptoms showed complete recovery over the subsequent six weeks, suggestive of para-infectious cerebellar demyelination due to mumps.

[Cerebellar syndrome after varicella infection without virus identification in cerebrospinal fluid--an important differential ataxia diagnosis]. / Zerebelläres Syndrom nach Varizelleninfektion ohne Virusnachweis im Liquor--eine wichtige Differentialdiagnose zur Ataxie.

We report on a 35 year old female with a 26 day history of an intermittent cerebellar syndrome (dysarthria, ataxia of extremities, gait and trunk, nystagmus), mild meningism, cephalgia, recurrent emesis and nausea. Symptoms developed after typically chickenpox exanthema. Examination of the liquor showed mild pleocytosis, elevated protein and increased albumin quotient. Virus was not found by EIA or PCR. There were elevated levels of IgM- and IgG-antibodies to VZV. The EEG showed mild general changes, compatible with an encephalitis. Neuroradiological examinations were unremarkful. The neurological deficits partly regressed in the follow-up of two months. To the best of our knowledge we are the first that describe the paradox of an intermittent cerebellar syndrome after infection with chickenpox without detection of the virus in the liquor. This phenomenon can be related to the unusual combination of cerebellar ataxia and the later occurrence of mild encephalitis.