Diffuse leptomeningeal histiocytic sarcoma in the cerebrospinal fluid of 2 dogs.

Two adult male castrated dogs were evaluated for progressive paraparesis and ataxia. Neurologic examination showed severe ataxia, delayed proprioceptive placement in the pelvic limbs, pain upon palpation of the lumbar spine as well as facial paresis in one dog, and decreased withdrawal reflex of the pelvic limbs in the other dog. Magnetic resonance imaging (MRI) in both dogs showed diffuse meningeal and intramedullary lesions. However, no evidence of a mass was found. Biopsies could not be performed safely due to the location of the lesions. Cerebrospinal fluid (CSF) examination revealed an inflammatory pleocytosis associated with increased protein concentration and numerous large atypical round cells, often multinucleated. Nuclear fragmentation, micronuclei, and rare atypical mitoses were observed. Immunocytochemistry revealed CD1(+) and CD11c(+) staining, which, in concert with the morphology confirmed the diagnosis of histiocytic sarcoma (HS). Euthanasia was elected due to poor prognosis. Histopathologic examination showed diffuse spinal and meningeal infiltration with CD18(+) neoplastic cells, without any evidence of mass formation, which completed the diagnosis of diffuse leptomeningeal HS involving the brain and the spinal cord. Canine central nervous system (CNS) HS has been seldom reported in the literature, with only isolated cases identified on CSF cytology. The cases reported here are remarkable in describing a diffuse CNS leptomeningeal HS associated with neoplastic cells in the CSF of dogs without a tumor mass. These cases emphasize the potential critical importance of CSF analysis in providing an antemortem diagnosis of neoplasia in neurologic patients.

Ataxia aguda asociada a la infección por el virus herpes humano tipo 6 / Acute ataxia associated with a human herpesvirus 6 infection

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Ultrasound-guided atlanto-occipital puncture for cerebrospinal fluid analysis on the standing horse.

The atlanto-occipital site (AO) is convenient for retrieving an adequate volume and quality of cerebrospinal fluid (CSF) in the diagnosis of neurological disease in horses. However, general anaesthesia is not always possible for horses displaying severe neurological signs, or for economical reasons. The objectives of the present work were to determine the feasibility and safety of ultrasound-guided CSF puncture at the AO site on the standing horse. Seven horses (six healthy and one mildly ataxic) were sedated with acepromazine (0.02 mg/kg bodyweight intravenously or 0.04 mg/kg bodyweight intramuscularly) and detomidine (0.01 mg/kg bodyweight intravenously), and placed in stocks or in a recovery stall with the head kept on a headstand. Puncture was performed by ultrasonographic guidance with a parasagittal technique, as previously described, using a 20 g, 3.5 inch spinal needle. In all horses, no adverse reaction was observed when crossing the dura mater and 20 ml of CSF was rapidly retrieved without any blood contamination. Ultrasound-guided CSF puncture can be performed easily at the AO site on a healthy standing horse. Regarding the potential risk of this procedure, safety measures and close observation are essential. Further studies on a larger amount of ataxic horses are also required before considering this technique as an alternative option for CSF puncture.

Encephalitis and GABAB receptor antibodies: novel findings in a new case series of 20 patients.

OBJECTIVE: To report the clinical features of 20 newly diagnosed patients with GABAB receptor (GABABR) antibodies and determine the frequency of associated tumors and concurrent neuronal autoantibodies. METHODS: Clinical data were retrospectively obtained and evaluated. Serum and CSF samples were examined for additional antibodies using methods previously reported. RESULTS: Seventeen patients presented with seizures, memory loss, and confusion, compatible with limbic encephalitis (LE), one patient presented with ataxia, one patient presented with status epilepticus, and one patient presented with opsoclonus-myoclonus syndrome (OMS). Nineteen (95%) patients eventually developed LE during the course of the disease. Small-cell lung cancer (SCLC) was identified in 10 (50%) patients, all with LE. Treatment and outcome was available from 19 patients: 15 showed complete (n = 7) or partial (n = 8) neurologic improvement after steroids, IV immunoglobulins, or plasma exchange and oncologic treatment when indicated; 1 patient died of tumor progression shortly after the first cycle of immunotherapy, and 3 were not treated. Five patients with SCLC had additional onconeuronal antibodies (Ri, amphiphysin, or SOX1), and 2 without tumor had GAD65 and NMDAR antibodies, respectively. GABABR antibodies were not detected in serum of 116 patients with SCLC without neurologic symptoms. CONCLUSION: Our study confirms GABABR as an autoantigen of paraneoplastic and nonparaneoplastic LE and expands the phenotype of GABABR antibodies to ataxia, OMS, and status epilepticus. The long-term prognosis is dictated by the presence of a tumor. Recognition of syndromes associated with GABABR antibodies is important because they usually respond to treatment.

Progressive ataxia and myoclonic epilepsy in a patient with a homozygous mutation in the FOLR1 gene.

Several unrelated disorders can lead to 5-methyltetrahydrofolate (5MTHF) depletion in the cerobrospinal fluid (CSF), including primary genetic disorders in folate-related pathways or those causing defective transport across the blood-CSF barrier. We report a case of cerebral folate transport deficiency due to a novel homozygous mutation in the FOLR1 gene, in an effort to clarify phenotype-genotype correlation in this newly identified neurometabolic disorder. A previously healthy infant developed an ataxic syndrome in the second year of life, followed by choreic movements and progressive myoclonic epilepsy. At the age of 26 months, we analyzed CSF 5MTHF by HPLC with fluorescence detection and conducted magnetic resonance (MR) imaging and spectroscopy studies. Finally, we performed mutational screening in the coding region of the FOLR1 gene. MR showed a diffuse abnormal signal of the cerebral white matter, cerebellar atrophy and a reduced peak of choline in spectroscopy. A profound deficiency of CSF 5MTHF (2 nmol/L; NV 48-127) with reduced CSF/plasma folate ratio (0.4; NV 1.5-3.5) was highly suggestive of defective brain folate-specific transport across the blood-CSF/brain barrier. Mutation screening of FOLR1 revealed a new homozygous missense mutation (p.Cys105Arg) that is predicted to abolish a disulfide bond, probably necessary for the correct folding of the protein. Both parents were heterozygous carriers of the same variant. Mutation screening in the FOLR1 gene is advisable in children with profound 5MTHF deficiency and decreased CSF/serum folate ratio. Progressive ataxia and myoclonic epilepsy, together with impaired brain myelination, are clinical hallmarks of the disease.

A case of progressive ataxia followed by cognitive and behavioral changes.

The patient is a 60-year-old man who initially presented to his local hospital with complaints of gait difficulties that started suddenly after waking. Results of brain magnetic resonance imaging performed 1 week later were normal. Three weeks after that he developed blurred vision and he complained of a severe headache in the posterior head and neck regions at the onset of symptoms, which necessitated several visits to his local emergency room. The patient presented to our institution 1 month later, with progressive gait difficulty and truncal instability over a 2-week period.

Progressive myoclonic ataxia with intrathecal immune activation in six patients.

In six patients with slowly progressive sporadic cerebellar ataxia and cortical multifocal action myoclonus, cerebrospinal fluid (CSF) IgG index was persistently very high (1.2-6.7) and numerous oligoclonal bands were detected. Progressive cognitive impairment and MRI cerebellar and cerebral atrophy were observed. No serum antibodies were found. Various degenerative, metabolic, inflammatory and systemic diseases were excluded. The cerebellum may be the main target of a degenerative or immune process and releases antigens that, enhancing a compartmentalised (auto)immune response, as suggested by the persistent intrathecal activation, could lead to further cerebellar damage. As the frequency of CSF oligoclonal banding in myoclonic ataxia is unknown, our patients' disease might represent a hitherto unreported entity or a subset of progressive myoclonic ataxia.

Decreased asialotransferrin in cerebrospinal fluid of patients with childhood-onset ataxia and central nervous system hypomyelination/vanishing white matter disease.

BACKGROUND: A biomarker for the diagnosis of childhood-onset ataxia and central nervous system hypomyelination (CACH)/vanishing white matter disease (VWM) would have clinical utility and pathophysiologic significance. METHODS: We used 2-dimensional gel electrophoresis/mass spectrometry to compare the cerebrospinal fluid proteome of patients with mutation-confirmed CACH/VWM with that of unaffected controls. We characterized selected spots by in-gel digestion, matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry, and nanospray Fourier transform mass spectrometry. RESULTS: A specific transferrin spot pattern was detected in the CSF samples of the CACH/VWM group (n = 7), distinguishing them from the control group (n = 23) and revealing that patients with CACH/VWM have a deficiency of the asialo form of transferrin usually present in healthy cerebrospinal fluid. The glycopeptide structure, determined from isolated transferrin spots by use of in-gel digestion and extraction, was found to be consistent with earlier reports. CONCLUSIONS: The transferrin isoform abnormality in the cerebrospinal fluid of patients with CACH/VWM appears unique and is a potential clinical diagnostic biomarker. The rapid, efficient diagnosis of this disorder would have a significant impact on clinical studies exploring new strategies for the management and treatment of this disease.

Opsoclonus-myoclonus-dysequilibrium syndrome: cytological and immunological dynamics in the serial cerebrospinal fluid in two patients.

A peculiar clinical presentation characterized by the triad of opsoclonus,myoclonus and ataxia, mainly in a form of dysequilibrium, is usually associated with infectious or paraneoplastic processes. Serial cerebrospinal fluid (CSF) analysis in two patients with opsoclonus-myoclonus-dysequilibrium syndrome suggestive of viral encephalitis were performed from disease onset for up to 8 months. A cell count, cytology, total protein and glucose concentrations in CSF, the blood-CSF barrier function, intrathecal synthesis of immunoglobulins (Ig) in class M, G and A expressed as IgM, IgG and IgA indices and oligoclonal IgG bands were monitored. Cellular and humoral alterations in both patients were slight at the onset becoming more pronounced a month later. The kinetics of the CSF changes mirrored the subacute clinical deterioration and subsequent recovery. The delayed response in the CSF measures and the gradual clinical deterioration suggest the development of subacute brain inflammation. A mononuclear pleocytosis, including macrophages and plasma cells, increased within the first month and then normalized during the following weeks. Intrathecally synthesized IgM occurred only transiently after one month of illness, whereas intrathecal IgG production increased during the first month and persisted for at least eight months. An increasing number of oligoclonal IgG bands during the course, indicative of expanding local intrathecal synthesis, was noted. The dynamics of these CSF changes supports the hypothesis that opsoclonus-myoclonus syndrome is a post-infectious immune- mediated condition.

Differences in total protein concentration, nucleated cell count, and red blood cell count among sequential samples of cerebrospinal fluid from horses.

OBJECTIVE: To examine total protein concentration and cell counts of sequentially collected samples of CSF to determine whether blood contamination decreases in subsequent samples and whether formulas used to correct nucleated cell count and total protein concentration are accurate. DESIGN: Case series. ANIMALS: 22 horses. PROCEDURE: For each horse, 3 or 4 sequential 2-ml samples of CSF were collected from the subarachnoid space in the lumbosacral region into separate syringes, and blood was obtained from the jugular vein. Total protein concentration, nucleated cell count, and RBC counts were determined in all samples. RESULTS: Among 3 sequential samples, total protein concentration and RBC count were significantly lower in samples 2 and 3, compared with sample 1. Nucleated cell count was significantly lower in sample 3, compared with sample 1. Among 4 sequential samples, total protein concentration and RBC count were significantly lower in samples 2, 3, and 4, compared with sample 1. Nucleated cell count was significantly lower in samples 3 and 4, compared with sample 1. For 3 correction formulas, significant differences in corrected values for nucleated cell count and total protein concentration were detected between sample 1 and sample 3 or 4. CONCLUSIONS AND CLINICAL RELEVANCE: Because iatrogenic blood contamination decreases in sequential CSF samples, a minimum of 3 samples should be collected before submitting the final sample for analysis. Formulas to correct nucleated cell count and total protein concentration are inaccurate and should not be used to correct for blood contamination in CSF samples.

An apparent case of human T-cell lymphotropic virus type II (HTLV-II)-associated neurological disease: a clinical, molecular, and phylogenetic characterisation.

Several studies have reported an association between HTLV-II and a neurological condition which has come to be called HTLV-II-associated myelopathy and is similar, in some cases, to HTLV-I-associated myelopathy. To further explore the establishment of an etiological link between this virus and neurological disease, we determined the HTLV status of three individuals, one of which presented with symptoms of progressive ataxia. Since the patient with neurological disease and her husband were HTLV-II positive, we had the potential to study one of few cases of an HTLV-II-associated neurological disorder, and the first case in Canada. However, although the individual with the neurological disease was HTLV-II positive, we discovered that her brother, who displays the same clinical symptoms, was not positive for either HTLV-II or HTLV-I. Thus, disease association with HTLV-II became unsupportable. We present here, nevertheless, the first sequence and phylogenetic analysis of an HTLV-II isolate in Canada. This study suggests that cases of HTLV-II and neurological disease must be carefully investigated before any etiological conclusions can be made.

Antineuronal antibody in a patient with neuroblastoma and opsoclonus-myoclonus-ataxia: a case report.

We describe a case of a patient with neuroblastoma and opsoclonus- myoclonus ataxia displaying serum and CSF anti-Hu antibodies that were able to recognize antigens of the patient's own tumor.

Biogenic amine metabolites in the CSF of patients with late onset and alcoholic ataxias.

The levels of monoamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG) and 5-hydroxyindoleacetic acid (5-HIAA) were measured in lumbar cerebrospinal fluid (CSF) from 10 patients with late onset ataxia, 8 patients with alcoholic ataxia and 18 control patients. The levels did not differ significantly among the three groups of patients suggesting that the central neuronal systems utilizing dopamine, noradrenaline and 5-hydroxytryptamine do not have a significant pathophysiological role in these forms of ataxias. The measurement of CSF amine metabolites probably does not contribute to the differential diagnosis of ataxias.

Electrophysiological study of four patients with Fisher syndrome: a mechanism of areflexia.

Electrophysiological studies were performed on four patients with the Fisher syndrome (two 4-year-old boys, a 5-year-old boy and a 9-year-old girl). Motor nerve conduction velocity (MNCV), nerve action potential, F wave, H reflex and T reflex were measured at the stage when areflexia was present but ataxia and ophthalmoplegia had recovered. MNCV and SNCV by compound mixed nerve potential were normal in all our patients. The amplitude of the muscle responses (M-responses) and compound mixed nerve action potentials were also within normal limits. The latencies of the F waves and F wave conduction velocities were normal. However, H-reflexes and T-reflexes were absent in all four cases. Our results suggested that areflexia in the Fisher syndrome is attributed to the desynchronization of the impulses or the partial conduction block of GIa fibers.

[Intracytoplasmic eosinophilic inclusions in dorsal root ganglia and spinal nerve roots from an autopsy case of unusual familial ataxia with cerebrospinal fluid abnormality].

Studies were performed on the light and electron microscopic structures of the dorsal root ganglia (DRG) and spinal nerve roots of the 4th lumbar nerve obtained by autopsy from a 49-year-old man with unusual familial ataxia, who showed varied neurological manifestations such as progressive ataxia, action tremors, pyramidal tract signs, mild deep sensory disturbances and autonomic dysfunctions during a 30-year period of illness, and had 2 siblings, one male and female, similarly affected and close consanguineous marriages in his family. On laboratory examinations, blood chemistry disclosed no significant findings. Repeated spinal taps showed constant xanthochromia and elevated protein in the cerebrospinal fluids. A PEG and cranial CTs revealed a progressive brain atrophy. NCVs and EMGs in the extremities were within normal limits. There was no chromosomal abnormality. Light microscopically, intracytoplasmic eosinophilic inclusions (IEIs) with pale rim, which showed varied sizes and rounded shapes, occurred within neurons in the DRG, particularly in small neurons. Many of the small neurons had numerous IEIs, and several rounded granules with a high degree of eosinophilia, measuring below 5 microns in diameter. Generally the small neurons showed atrophic, while most large neurons showed no remarkable change although they had a small number of IEIs and granules located in the perikaryal periphery. Most satellite cells, and some Schwann cells in the DRG, ventral and dorsal roots had IEIs similar to those seen in the neurons. No IEIs occurred intraaxonally, and there was seen no degenerative process in the DRG and roots except a connective tissue fiber proliferation in the DRG.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebrospinal fluid eosinophilia and ataxia in five llamas.

Cerebrospinal fluid eosinophilia was associated with ataxia in five llamas. A presumptive diagnosis of cerebrospinal parasitism was made, and a response to combined anthelmintic and anti-inflammatory therapy was seen in each animal. The results demonstrate the value of an examination of cerebrospinal fluid in the evaluation of neurological disease in llamas.

Reduction of biogenic amine levels in the Rett syndrome.

The Rett syndrome is a progressive disorder in female patients that is characterized by autistic behavior, dementia, ataxia, loss of purposeful use of the hands, and seizures. The results of laboratory investigations are usually normal, with the exception of electroencephalography. In an attempt to understand the pathogenesis of this syndrome, we assayed biogenic amine metabolites in the cerebrospinal fluid of six patients, 2 to 15 years of age. 3-Methoxy-4-hydroxyphenylethylene glycol (MHPG, a metabolite of norepinephrine), homovanillic acid (a metabolite of dopamine), and 5-hydroxyindoleacetic acid (5-HIAA, a metabolite of serotonin) were quantitated by a method involving gas chromatography and mass spectrometry. Levels of MHPG and homovanillic acid were significantly reduced in all the patients as compared with those in controls of similar age (P = 0.01 and 0.008, respectively). The reduction in the level of 5-HIAA was not significantly different from that in the controls (P = 0.15). These findings suggest an underlying disorder of biogenic amines in the Rett syndrome and may provide new insight into its pathogenesis.