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BackgroundAutosomal dominant spinocerebellar ataxia type 1 is an adult onset progressive disorder with well characterized neurodegeneration in the cerebellum and brainstem. Beyond brain atrophy, few data exist concerning retinal and optic nerve involvement.Objective To evaluate retinal changes in SCA1 patients compared to age and gender matched healthy controls.Methodology/Principal FindingsNine patients with SCA1 were prospectively recruited from the ataxia clinic and were compared to nine age and gender matched healthy controls. Both cohorts received assessment of visually evoked potentials and eye examination by optical coherence tomography to determine retinal nerve fiber layer thickness and total macular volume. While no differences were found in visually evoked potentials, SCA1 patients showed a significant reduction of mean retinal nerve fiber layer thickness (RNFLT) compared to healthy controls (84±13 µm vs. 97±8 µm, p = 0.004). Temporal areas showed the most prominent RNFLT reduction with high statistical significances (temporal-inferior: p<0.001, temporal: p<0.001, temporal-superior: p = 0.005) whereas RNFLT in nasal areas was in the range of the control group. From six SCA1 patients an additional macular scan was obtained. The comparison to the corresponding healthy control showed a slight but not significant reduction in TMV (8.22±0.68 mm3 vs. 8.61±0.41 mm3, p = 0.15).ConclusionIn SCA1 patients, we found evidence for degeneration of retinal nerve fibers. The temporal focus of the observed retinal nerve fiber layer reduction suggests an involvement of the papillo-macular bundle which resembles pathology found in toxic or mitochondrial optic nerve disease such as Leber's hereditary optic neuropathy (LHON) or dominant optic atrophy (DOA).

Apart from potential roles in anti-tumor surveillance, the TNF-related apoptosis-inducing ligand (TRAIL) has important regulatory functions in the host immune response. We studied antiinflammatory effects of endogenous and recombinant TRAIL (rTRAIL) in experimental meningitis. Following intrathecal application of pneumococcal cell wall, a TLR2 ligand, we found prolonged inflammation, augmented clinical impairment, and increased apoptosis in the hippocampus of TRAIL -/-mice. Administration of rTRAIL into the subarachnoid space of TRAIL -/-mice or reconstitution of hematopoiesis with wild-type bone marrow cells reversed these effects, suggesting an autoregulatory role of TRAIL within the infiltrating leukocyte population. Importantly, intrathecal application of rTRAIL in wild-type mice with meningitis also decreased inflammation and apoptosis. Moreover, patients suffering from bacterial meningitis showed increased intrathecal synthesis of TRAIL.Our findings provide what we believe is the first evidence that TRAIL may act as a negative regulator of acute CNS inflammation. The ability of TRAIL to modify inflammatory responses and to reduce neuronal cell death in meningitis suggests that it may be used as a novel antiinflammatory agent in invasive infections.

Fatigue is one of the most frequent and disabling symptoms in multiple sclerosis (MS). Its pathophysiology remains poorly understood and objective measures to quantify fatigue are unavailable to date. To investigate whether analysis of ocular motor movements can provide diagnostic information in MS patients with fatigue, 37 MS patients (21 female, age 44 ± 9 years) and 20 age- and gender-matched healthy controls were prospectively recruited. Fatigue was assessed with the fatigue severity scale (FSS). Twenty-five MS patients were fatigued (defined as FSS ≥ 4) and 12 MS patients were not. Subjects performed a saccadic fatigue task that required execution of uniform saccades over a period of 10 min. Saccadic amplitude, latency and peak velocities during the task were analysed and selected parameters were tested in a receiver operating characteristic (ROC) analysis. Fatigued patients showed a significantly larger decrease of saccadic peak velocity and amplitude when compared to patients without fatigue and healthy controls. Furthermore, fatigued patients showed significantly longer latencies compared to non-fatigued patients and healthy controls. Peak velocity change over time and latencies correlated with FSS scores. The best parameter to discriminate between fatigued and non-fatigued patients was peak velocity change over time (ROC; area under the curve = 0.857). Assessment of peak velocity, amplitude and latency in a saccade fatigue task is a promising approach for quantifying fatigue in MS patients.

OBJECTIVE The authors’ objective was to study clinical, imaging, and neuropsychological changes in children who underwent surgery for a temporal arachnoid cyst (TAC). METHODS Thirty-four children were prospectively assessed similarly at diagnosis and postoperatively (mean 14 months) with clinic visits, images, cognitive tests, and parental questionnaires on mood/behavior and executive functions. The scores were compared pre- and postoperatively for the entire cohort and individually. The scores of 25 children were also compared with a control group of 23 healthy age-matched children. Parents were administered an outcome questionnaire on average 4 years postoperatively. RESULTS The 34 children selected for surgery had signs of raised intracranial pressure (74%) and/or selective neuropsychological disorders presumably linked to cyst location (learning difficulties in 65%, cognitive difficulties in 56%, and mood/behavior difficulties in 47%). The majority of patients had a convex cyst (85%) and underwent microsurgical fenestration (85%). The TAC volume decreased ≥ 50% for 59% of children. On the Wechsler Intelligence Scale, the entire cohort significantly improved on Full Scale IQ and verbal and perceptual nonverbal indexes. Individually, nearly half of the children (47%) highly increased their scores (≥ 15 points) on at least one IQ index and 26% on at least two indexes. Language, working memory, episodic memory, and executive functions were also significantly improved. Improvements were more pronounced in patients with a preoperative heterogeneous profile with isolated lower scores and a left-sided cyst. Parental questionnaires showed reduction in anxiety, aggressiveness, social problems, and daily life executive disorders. Preschool-aged children improved significantly in language and verbal IQ, as did middle/high school–aged children in many domains. Individual analyses revealed improvement in 76% of cases. Cognitive scores were lower for patients preoperatively than for controls and were no longer significantly different postoperatively in verbal fluency, visual memory, and working memory. Four years later, 97% of parents described an improvement in their child, correlated with cognitive improvements. CONCLUSIONS Among children with a TAC, some have no clinical signs or neuropsychological difficulties, and others may show signs of raised intracranial pressure and/or specific neuropsychological disorders that impact daily life and require significant and long-lasting rehabilitation. In these cases, consideration may be given to surgical decompression. It is interesting to note that 76% of this surgically treated cohort improved regardless of the child’s age, particularly in patients with selective disorders and an impact on daily life. However, a larger number of children will need to be investigated before the true benefit of such treatment can be known.