Paraneoplastic cerebellar degeneration. III. Cerebellar degeneration, cancer, and the Lambert-Eaton myasthenic syndrome.

We studied nine patients with a subacute onset of a pancerebellar syndrome. Six had known cancer (three small-cell carcinoma of the lung [SCLC], one metastatic small-cell carcinoma, one small-cell carcinoma of the prostate, and one non-Hodgkin's lymphoma). Six of eight who had neurophysiologic testing, including the three patients without detectable cancer, had coexistent Lambert-Eaton myasthenic syndrome (LEMS). In two of the patients, LEMS was discovered only by neurophysiologic testing. We looked for anti-Purkinje cell autoantibodies in all patient's sera and in four patients' CSF. We also looked for autoantibodies to voltage-gated calcium channels (VGCCs) in seven patients' sera and two patients' CSF, using the 125I-omega-conotoxin radioimmunoassay. We were unable to detect anti-Purkinje cell autoantibodies in any patients' serum or CSF. However, there were raised titers of anti-VGCC autoantibodies in five of seven patients' serum, including one patient with SCLC who did not have LEMS, and in the CSF of one of two patients. We conclude that the frequency of presentation of a pancerebellar syndrome with LEMS is higher than expected by chance and is usually associated with cancer. In some of these patients, LEMS may be clinically occult. The presence of LEMS and raised titers of anti-VGCC autoantibodies in some patients with subacute cerebellar degeneration is suggestive of an autoimmune etiology even though anti-Purkinje cell antibodies could not be detected. Anti-VGCC autoantibodies are not confined to LEMS. They may be found at high titer in CSF as well as serum.     

Functional activity of auditory cortex studied with SPECT: methodology validation and application in bilateral profound deafness

To evaluate the differences in the functional activity of the auditory cortex between normal hearing and profound deafness, a perfusion single photon emission tomography (SPECT) study was designed. SPECT stereotaxic localisation of the auditory cortex was previously validated in 2 brains by means of an anatomical study of the macroscopic localisation and cytoarchitecture of the auditory cortex. Additionally, 15 controls with normal hearing and 30 patients with profound bilateral deafness were scanned using external anatomical point sources (glabela, ineon) for stereotaxic location of the auditory cortex. The normal controls were scanned in auditive deprivation and, in 10 cases, during a monoaural tonal stimulation. Cerebral blood flow relative to cerebellum (relCBF) was assessed in the auditory cortex. The anatomical study showed that mean differences between the true auditory cortex size and the measured SPECT value were less than 2.5 mm. Nevertheless, only the caudal aspect of this area corresponded to the primary auditory cortex in the cytoarchitectonic study. During tonal stimulation, control subjects presented a significant increase of relCBF in the auditory cortex bilaterally, with significant differences in the asymmetry index (contralateral to the side of stimulation). The relCBF in the auditory cortex of controls in deprivation conditions was significantly higher than in deaf patients. There were no significant differences between groups of deaf patients, however the highest values were seen after cochlear implant. SPECT is a suitable method for studying changes in auditory cortex activity relative to different functional conditions, with a possible role in cochlear implant candidates in predicting the future benefit of the implantation.     

Hirschsprung's disease associated enterocolitis: A comprehensive review

Hirschsprung’s disease (HSCR) is a congenital disorder characterized by failure of the neural crest cells to migrate and populate the distal bowel during gestation affecting different lengths of intestine leading to a distal functional obstruction. Surgical treatment is needed to correct HSCR once the diagnosis is confirmed by demonstrating the absence of ganglion cells or aganglionosis of the affected bowel segment. Hirschsprung’s disease associated enterocolitis (HAEC) is an inflammatory complication associated with HSCR that can present either in the pre- or postoperative period and associated with increased morbidity and mortality. The pathogenesis of HAEC remains poorly understood, but intestinal dysmotility, dysbiosis and impaired mucosal defense and intestinal barrier function appear to play a significant role. There is no clear definition for HAEC, but the diagnosis is primarily clinical, and treatment is guided based on severity. Here, we aim to provide a comprehensive review of the clinical presentation, etiology, pathophysiology, and current therapeutic options for HAEC.     

Neuroimaging as a marker of the onset and progression of Alzheimer's disease

Several neuroimaging techniques are promising tools as early markers of brain pathology in Alzheimer's disease (AD). On structural MRI, atrophy of the entorhinal cortex is present already in mild cognitive impairment (MCI). In the autosomal dominant forms of AD, the rate of atrophy of medial temporal structures separates affected from control persons even 3 years before the clinical onset of cognitive impairment. The elevated annual rate of brain atrophy offers a surrogate tool for the evaluation of newer therapies using smaller samples, thereby saving time and resources. On functional MRI, activation paradigms activate a larger area of parieto-temporal association cortex in persons at higher risk for AD, whereas the entorhinal cortex activation is lesser in MCI. Similar findings have been detected with activation procedures and water (H(2)(15)O) PET. Regional metabolism in the entorhinal cortex, studied with FDG PET, seems to predict normal elderly who will deteriorate to MCI or AD. SPECT shows decreased regional perfusion in limbic areas, both in MCI and AD, but with a lower likelihood ratio than PET. Newer PET compounds allow for the determination in AD of microglial activation, regional deposition of amyloid and the evaluation of enzymatic activity in the brain of AD patients.     

Sustained attention in a counting task: normal performance and functional neuroanatomy

We examined changes in relative cerebral flood flow (relCBF) using PET during a sustained attention paradigm which included auditory stimulation and different tasks of mental counting. Ten normal volunteers underwent PET (15O water) during a baseline state and under experimental conditions which included listening to clicks, serial counting with auditory stimulation, counting with no auditory stimulation, and an additional component of working memory and time estimation. All subjects performed within normal limits in a battery of neurocognitive tests, which included measures of attention and working memory. Both counting with auditory stimulation and counting with no auditory stimulation engaged motor cortex, putamen, cerebellum, and anterior cingulate. Furthermore, counting with no auditory stimulation relative to counting while listening resulted in significantly increased relCBF in the inferior parietal, dorsolateral prefrontal, and anterior cingulate. The findings obtained in this study support the notion that the parietal and dorsolateral prefrontal cortex are involved when time estimation and working memory are taking part in a task requiring sustained attention.     

An approach to estimating the intangible costs of multiple sclerosis according to disability in Catalonia, Spain

Multiple sclerosis (MS) is a chronic demyelinating disease, which represents a great economic burden to society. Cost-of-illness studies of MS tend to underestimate the intangible costs related to pain, anxiety and helplessness. The purpose of this study was to estimate the intangible costs of MS, and determine whether these costs increase as disability progresses. We studied 211 consecutive patients with MS who attended our MS unit. Patients mean age was 41.6 (SD: 10.7) years, 69% were female, and their mean Expanded Disability Status Scale (EDSS) score was 2.47 (SD: 2.05). Quality-of-life was measured with the EuroQoL visual analogue scale. Quality-adjusted life year (QALY) was calculated for each patient. Patients were grouped into five disability stages according to their EDSS, and QALY was compared between patients and a group of healthy controls matched by age and sex. A benchmark value was ascribed to each QALY lost, and the intangible costs per patient-year were calculated as Euros 0 (EDSS =0), Euros 1100 (EDSS =1-3), Euros 8250 (EDSS =3.5-5.5), Euros 9900 (EDSS =6-7) and Euros 11,000 (EDSS >7.5). Sensitivity analysis showed a similar progression of costs. We conclude that intangible costs are relevant in MS, especially when disability increases. Although the method to calculate the costs remains controversial, we consider that they should be included in cost analysis of MS.