A novel PSEN2 mutation associated with a peculiar phenotype.

BACKGROUND: Mutations of presenilin 2 gene are a rare cause of familial Alzheimer disease (AD). We describe an Italian family with hereditary dementia associated with a novel mutation in the presenilin 2 gene. METHODS: Clinical investigations of the diseased subjects; interviews with relatives; studies of medical records; pedigree analysis; and neuroradiologic, neuropathologic, and molecular genetic studies were carried out in the pedigree. RESULTS: Genetic analysis showed a novel PSEN2 A85V mutation present in the proband and in all analyzed affected members, in a subject presenting with an amnesic mild cognitive impairment, and in a young, still asymptomatic subject. The proband showed a clinical phenotype indicative of Lewy body dementia and the neuropathologic examination demonstrated the presence of unusually abundant and widespread cortical Lewy bodies in addition to the hallmark lesions of AD. Other affected members exhibited a clinical phenotype typical of AD. CONCLUSIONS: Our findings add complexity to the spectrum of atypical phenotypes associated with presenilin mutations and should then be taken into account when considering the nosography of neurodegenerative diseases. They also support previous data that specific mutations of genes associated with familial Alzheimer disease may influence the presence and extent of Lewy bodies.

Cognitive impairment and neurophysiological correlates in MS.

Cognitive impairment in multiple sclerosis (MS) has received considerable interest over the last decades. Heterogeneous patterns of cognitive dysfunction have been reported in literature in relation to the subtype of the disease and the severity of specific cognitive domains affected. Event related potentials (ERPs), especially P300, have been employed to evaluate the cognitive decline in MS and neurophysiological findings agree with data obtained by neuropsychological testing. The objectivity, the reliability and the easy administration are the main features of ERP technique but more specific attention and memory tasks are needed to enhance the clinical value of the methodology. Moreover, ERP recording has the advantage of being feasible even in severe disabled patients. Finally, longitudinal ERP studies are required to investigate the natural course of cognitive dysfunction in MS, to estimate the prognostic value of subclinical defects in different clinical form of the disease and to evaluate clinical benefits of therapeutic and rehabilitative interventions.

Longitudinal study of cognitive dysfunction in multiple sclerosis: neuropsychological, neuroradiological, and neurophysiological findings.

OBJECTIVE: (1) To assess cognitive function and cerebral magnetic resonance imaging (MRI) involvement in relapsing-remitting multiple sclerosis; (2) to monitor disease evolution, cognitive dysfunction, and cerebral lesion burden over time (mean 8.5 year follow up period); (3) to study the relation between clinical, neuropsychological, and MRI data. On follow up assessment, visual and auditory oddball event related potentials (ERPs) were recorded as psychophysiological evaluation of cognitive status. Correlations between neuropsychological, MRI, and ERP data were also analysed. METHODS: Neuropsychological study assessed verbal and non-verbal IQ, deterioration index (DI) from WAIS subtests, conceptual reasoning, attention, verbal and visuospatial short-term and long term memory. MRI assessment detected presence of demyelinating lesions by using a semiquantitative method as well as cortical and subcortical atrophy over time. RESULTS: Attention, short-term and long term visuospatial memory were mildly impaired at baseline and remained unaltered longitudinally. At retesting a significant worsening of verbal long term memory (p=0.023), DI presence (p=0.041) and the increase of supratentorial and subtentorial MRI lesions load (p=0.001) emerged. Expanded disability status scale score correlated significantly with total lesion burden at both evaluations (p=0.043 and p=0.024 respectively). Temporal, occipital, and frontal horn lesions as well as cortical atrophy correlated significantly with attention and memory tests at baseline. Follow up assessment revealed significant correlation between cortical atrophy and attention as well as visuospatial short-term memory; spatial long term memory correlated significantly with lesions in body of lateral ventricle and frontal lobe. ERP study showed P300 latency abnormalities in 75% of patients, involving specifically more visual P300 (58.4 % of cases) than auditory wave (41.6 %). Visual P300 latency and amplitude correlated significantly with DI and auditory P300 latency with frontal horn and brain stem lesions. CONCLUSIONS: These findings revealed mild cognitive impairment in MS patients particularly consistent with slowing information processing over time. Increased MRI lesions do not correlate with the clinical course of the disease and cognitive deficit evolution. Thus, cognitive dysfunction could be related to disease peculiarity and not to the time course. Correlations between P300, neuropsychological, and MRI findings provide further information about ERP application to examine cognitive impairment in MS and probably to investigate their neural origin.

Visual and auditory event-related potentials in sporadic amyotrophic lateral sclerosis.

OBJECTIVES: To investigate the relationship between amyotrophic lateral sclerosis (ALS) and cognitive function by means of oddball event-related potentials (ERPs) and to determine the usefulness of this methodology in the cognitive status assessment of physically disabled patients. METHODS: Visual and auditory oddball ERPs were recorded in 16 consecutive sporadic ALS patients. A comprehensive battery of neuropsychological (NP) tests assessed intelligence, executive functions, attention, memory, word fluency, visuo-motor and visual-constructive skills. RESULTS: All patients performed visual and auditory ERPs and 75% of cases showed abnormal N200 and/or P300 waves. Ten patients (62.5%) carried out the entire psychometric evaluation with significant impairment on tests of executive function and attention. A significant correlation between delayed visual (P<0.04) and auditory (P<0.04) P300 latency and impaired NP tests was found. CONCLUSIONS: In agreement with literature data, our findings confirm the hypothesis of cognitive impairment in ALS patients especially on attention and executive functions suggesting a more extensive degeneration beyond the motor areas. ALS causes severe physical disabilities and such a condition may interfere with NP testing. Thus, the P300 seems to be a useful tool for the assessment of cognition and attention when severe physical deficits are present.

P300 and executive function alterations: possible links in a case of Morgagni-Stewart-Morel syndrome.

To evaluate possible cause-effect relationships between hyperostosis frontalis interna and cognitive dysfunction, we performed a neurophysiological (event-related potentials, ERPs) and neuropsychological study in a case of Morgagni-Stewart-Morel (MSM) syndrome associated with frontal lobe compression. Neuropsychological evaluation evidenced selective impairment of executive function. Visual and auditory oddball ERPs revealed delayed P300 latency and reduced auditory P300 amplitude with multi-peaked morphology. ERP abnormalities and cognitive dysfunction could be due to the frontal bone-cortex conflict documented by neuroradiological investigations.

Clear cell hepatocellular carcinoma treated with liver transplantation.

We report a case of a 35-year-old female who underwent total hepatectomy and liver transplantation for a diffuse clear cell variant of hepatocellular carcinoma in non-cirrhotic liver. Preoperative clinical evaluation showed no extrahepatic metastatic involvement. However, scheletal metastases of the tumour were detected five months later. Although clear cell variant is generally considered to run a relatively favorable course, this case proved rapidly progressive and seems therefore to be a debatable candidate for liver transplantation among primary hepatic cancers.

Neuroborreliosis: a Sardinian case with cerebellar symptoms.

We report the case of a patient long resident in Sardinia in whom the clinical history, neurological symptoms, serological and neuroradiological investigations pointed to the diagnosis of neuroborreliosis. We emphasize the rarity of cerebellar involvement in this disease.

Phenobarbital-induced buccolingual dyskinesia in oral apraxia.

A young woman with oral apraxia and a well-defined brain lesion on CT scan developed buccolingual dyskinesia lasting 40 days after low phenobarbital (PB) doses. Disruption of the corticostriatal glutamatergic pathway from areas 6 and 4 may have been important both in causing oral apraxia and in lowering the threshold for PB-induced buccolingual dyskinesia.

Epidemiologic study of amyotrophic lateral sclerosis in Sardinia, Italy.

From 1957 to 1980 in Sardinia, 182 cases of ALS with a mean annual incidence of 0.51 per 100,000 inhabitants and a prevalence rate of 3.65 per 100,000 inhabitants (prevalence day 21.10.1971) were observed. The disease was found to be more common in males, in subjects aged 50 to 70 years and in farmers and shepherds. Incidence in various areas of the island was found to be different. The common form was more frequent, had earlier onset and greater median survival rate.

Brain atrophy, peripheral neuropathy and folic acid deficiency.

A woman with peripheral neuropathy and cerebral atrophy, both secondary to a selective folic acid deficiency caused by severe gastrointestinal disturbances, was given folic acid replacement therapy, which improved her clinical, blood and neurophysiological status.

[Serum gastrin in rheumatoid arthritis]. / Gastrine sérique au cours de la polyarthrite rheuatoïde.

Serum gastrin concentrations under basal conditions and following stimulation were assessed in 40 patients suffering from rheumatoid arthritis (RA) and compared with healthy individuals. The RA groups showed no significant differences in comparison with the control population. These conclusions lead the authors to seek the reasons for the rare instances of confirmed hypergastrinaemia in RA.