Overlapping neuropathological findings in an asymptomatic SPAST gene mutation carrier.

Hereditary spastic paraparesis (HSP) caused by mutations in the SPAST (SPG4) gene are autosomal-dominant inherited disorders characterized by weakness of lower extremities, spasticity and hyperreflexia. Some cases with cognitive decline have been repored. Herein we present an asymptomatic carrier of a SPAST gene mutation who developed an adult-onset cognitive decline, compatible with Alzheimer's disease with co-pathologies such as argyrophylic grain disease and cerebrovascular pathology. No pathological changes described in HSP patients were present in this case.

Distinctive Olfactory Pattern in Parkinson's Disease and Non-Neurodegenerative Causes of Hyposmia.

BACKGROUND: Olfactory dysfunction is common in Parkinson's disease (PD). The characteristics of the hyposmia in PD have not been well defined. OBJECTIVE: To characterize the pattern of the olfactory deficit in PD and in other non-neurodegenerative aetiologies of hyposmia. METHODS: We evaluated 36 PD patients, 20 patients with hyposmia secondary to acute respiratory infection (ARI), and 19 patients with hyposmia secondary to traumatic brain injury (TBI). For comparison purposes, we included a group of 15 controls age and sex matched with PD patients. PD patients were classified based on disease duration and severity in de novo PD, and PD with and without chronic levodopa-related complications. The Barcelona Smell Identification Test was applied to all participants. RESULTS: For the first cranial nerve odours, PD patients scored lower than controls on smell detection (85.28 vs. 97.67%, p = 0.006), definition (79.58 vs. 93.33%, p = 0.007), recognition (63.33 vs. 81%, p = 0.020), and forced choice (58.06 vs. 82%, p < 0.001). Compared with ARI, forced choice was significantly better in PD patients (p < 0.001), but no differences were found regarding other olfactory characteristics. TBI patients showed significantly lower scores than the other study groups in all the olfaction items. For the fifth cranial nerve odours, recognition (p = 0.003) and identification (p = 0.019) were lower in the TBI group than in the others. No differences were found among PD subgroups regarding any olfactory characteristic. CONCLUSIONS: A differential pattern of hyposmia was observed in PD patients compared to other non-neurodegenerative aetiologies. Further studies with larger samples should replicate our results.

Third Ventricle Width Assessed by Transcranial Sonography as Predictor of Long-Term Cognitive Impairment.

BACKGROUND: Non-invasive biomarkers of cognitive impairment are needed. We aim to evaluate transcranial sonographic markers as predictors of cognitive impairment in a prospective cohort. OBJECTIVE: To study the changes in the third ventricle diameter and the SN echogenicity between the baseline and the control visit, as well as its association with cognitive performance and the diagnosis of cognitive impairment in a prospective cohort. METHODS: From the longitudinal population-based Asymptomatic Intracranial Atherosclerosis Study, we selected those subjects that received a complete transcranial sonography (TCS) and extensive cognitive testing, both at baseline and follow-up. We evaluated third ventricle (IIIv) width, echogenicity of substantia nigra (SN), and temporal changes of these parameters. RESULTS: We included 289 participants with a median follow-up time of 7.16 years. Those subjects who developed cognitive decline (n = 23, 7.96%) had a larger IIIv at baseline than those who did not (0.54±0.14 cm versus 0.41±0.15 cm; p = 0.001). A cut-off point of 0.465 cm for the IIIv width was identified as an independent predictor of long-term cognitive impairment after adjustment for age, gender, educational level, and vascular risk score. Change in IIIv diameter after follow-up was not associated with diagnosis of cognitive impairment. The area of SN and the presence of hyperechogenicity of the SN remained stable over time and was not associated with the diagnosis of cognitive impairment. CONCLUSION: IIIv width assessed by TCS emerged as an independent predictor of long-term cognitive impairment.

Progressive multifocal leukoencephalopathy associated to natalizumab extended dosing regimen.

A risk for developing progressive multifocal leukoencephalopathy is a major barrier to natalizumab use. Extended dosing intervals have been proposed as a way to maintain therapeutic efficacy and reduce progressive multifocal leukoencephalopathy incidence. This is the first reported case of progressive multifocal leukoencephalopathy in a patient using an extended dosing regimen (300 mg/6 weeks). A close clinical and imaging monitoring allowed early detection, which is a major prognostic factor. A favorable outcome was seen with a therapy comprising plasma exchange therapy, mirtazapine, mefloquine and cidofovir. Further studies will be needed to assess the potential role of extended dosing intervals to improve prognosis in patients receiving natalizumab and also to measure its impact clinically and/or radiologically.