Oculodentodigital dysplasia (ODDD) is a rare autosomal dominant congenital malformation syndrome characterized by high penetrance and great phenotypic heterogeneity. Neurological manifestations are thought to occur in about one third of cases, but systematic studies are not available. We performed deep neurological phenotyping of 10 patients in one ODDD pedigree. Retrospective case series. We analyzed in depth the neurological phenotype of a three-generation family segregating the heterozygous c.416 T > C, p.(Ile139Thr) in GJA1. Clinical and neuroradiological features were retrospectively evaluated. Brain MRI and visual evoked potentials were performed in 8 and 6 cases, respectively. Central nervous system manifestations occurred in 5 patients, the most common being isolated ataxia either in isolation or combined with spasticity. Furthermore, sphincteric disturbances (neurogenic bladder and fecal incontinence) were recognized as the first manifestation in most of the patients. Subclinical electrophysiological alteration of the optic pathway occurred in all the examined patients. Neuroimaging was significant for supratentorial hypomyelination pattern and hyperintense superior cerebellar peduncle in all examined patients. The neurological involvement in ODDD carriers is often missed but peculiar clinical and radiological patterns can be recognized. Deep neurological phenotyping is needed to help untangle ODDD syndrome complexity and find genotype–phenotype correlations.

Objective: Essential Tremor (ET) is one of the most common neurological disorders. In most instances ET is inherited as an autosomal dominant trait with age-related penetrance (virtually complete in advanced age); however, ET genetics remains elusive. The current study aims to identify possibly pathogenic genetic variants in a group of well-characterized ET families. Methods: 34 individuals from 14 families with dominant ET were clinically evaluated and studied by whole exome sequencing studies (after excluding trinucleotide expansion disorders). Results: Most patients had pure ET. In 4 families, exome studies could identify a genetic variant potentially able to significantly alter the protein structure (CADD >20, REVEL score > 0.25), shared by all the affected individuals (in CAMTA1 , FUS , MYH14, SGCE genes). In another family there were two variants in dominant genes ( PCDH9 and SQSTM1 ). Moreover, an interrupted "intermediate" trinucleotide expansion in ATXN1 ("SCA1") was identified in a further family with pure ET. Conclusion: Combining our observations together with earlier reports, we can conclude that ET genes confirmed in at least two families to date include CAMTA1 and FUS (reported here), as well as CACNA1G , NOTCH2NLC and TENM4. Most cases of familial ET, inherited with an autosomal dominant inheritance, may result from "mild" variants of many different genes that, when affected by more harmful genetic variants, lead to more severe neurological syndromes (still autosomal dominant). Thus, ET phenotype may be the "mild", incomplete manifestation of many other dominant neurogenetic diseases. These findings further support evidence of genetic heterogeneity for such disease(s).

The Movement Disorders Society (MDS) formulated diagnostic criteria and assessment guidelines for the screening of dementia in Parkinson's disease (PD). We carried out a validation of the cognitive measures suggested in the screening algorithm (i.e. the Mini Mental State Examination - MMSE - total score, serial 7s subtraction, 3-word recall, pentagons copy, and one minute letter fluency) in 86 patients with PD. Thirty-six percent of participants were diagnosed with dementia using the MDS algorithm, but with the Dementia Rating Scale instead of the MMSE. The original MDS procedure misclassified 11 patients (12.8%) as false negatives and 3 (3.5%) as false positives, leading to 65% sensitivity and 95% specificity. The main reason for misdiagnoses was insensitivity of the MMSE total score. Three attempts were made to reach a better screening performance, which warrants high sensitivity more than high specificity: 1. exclusion of the MMSE total score as a diagnostic requirement; 2. determination of a better cut off through Receiver Operating Characteristic curve analysis; 3. replacement of the MMSE with the equally undemanding, but more PD-specific, Mini Mental Parkinson. The first two strategies generally yielded high sensitivity, but poor specificity. The best outcome was achieved using a Mini Mental Parkinson total score <27 as cognitive criterion: sensitivity was 87% and negative predictive value was 90%; however, specificity was only 67%. Our findings seem to suggest that MDS practical guidelines are specific, but might benefit from the use of more PD-oriented tools than the MMSE in terms of sensitivity.

The detection of cognitive decline in Parkinson's disease (PD), at the Mild Cognitive Impairment (MCI) stage, has prognostic and treatment implications. The Movement Disorders Society (MDS) has recently published criteria and guidelines for the diagnosis of possible and probable PD-MCI. In the present study we assessed the ability of the Scales for Outcomes in Parkinson's disease-Cognition (SCOPA-Cog) to discriminate possible PD-MCI cases from patients with PD-dementia (PDD) and from cognitively intact PD subjects. Hundred-and-thirteen consecutive PD patients underwent the MMSE, the Dementia Rating Scale and an interview on independence in daily living, and were classified as cognitively intact (n = 49), or as possible PD-MCI (n = 33) or PDD (n = 31), according to MDS criteria. Logistic regression analysis was carried out with PD-MCI diagnosis (yes/no) as an outcome variable, and age, education and the SCOPA-Cog total score as covariates. Classification of cases according to the regression model was used for constructing Receiver Operating Characteristic (ROC) curves. Area Under the Curve (AUC) was 0.92 [95% CI 0.86-0.98], for the differential diagnosis between PD-MCI and cognitively normal patients, and 0.97 [95% CI 0.80-1.00], for the differential diagnosis between PD-MCI and PDD. Sensitivity and specificity were 90% and 73% for the PD-MCI versus no cognitive impairment differentiation, at the cutpoint >= 24, and 93% and 97% for the PD-MCI versus PDD discrimination, at the cutpoint >= 17. The SCOPA-Cog is a quick and psychometrically sound PD-specific scale. Our findings support its use for the screening of possible PD-MCI. (C) 2013 Elsevier Ltd. All rights reserved.

The MiniMental Parkinson (MMP) has been derived from the MiniMental State Examination (MMSE) for the screening of cognitive impairment in Parkinson’s disease by adding subtests that were focused on executive and visuo-spatial impairment more than on memory or language deficits. In this multicenter study, the psychometric and validity properties of the MMP have been evaluated in 69 cognitively intact and 52 cognitively impaired patients with Parkinson’s disease, classified according to their performance at the Dementia Rating Scale. The MMP showed better metrics and convergent validity, and higher screening ability. However, its performance was not fully satisfying in terms of data distribution, coefficient of variation and specificity, and Receiver Operating Characteristic curves did not show clear cut superiority of either scale at their best sensitivity–specificity trade off. The MMP seems to be slightly preferable to the MMSE only at a cut off that favours sensitivity with respect to specificity, for screening purposes. The test is simple and quick, but has limitations in terms of validity.

We report a patient with MELAS treated for 24 months with idebenone and riboflavin, during which no stroke-like episodes occured. Moreover neurological symptoms clearly improved, and a recovery of brain MRI and EEG abnormalities was observed. We conclude that the combined treatment with idebenone and riboflavin may restore the metabolic impairment in MELAS, possibly improving the long-term prognosis in these patients.

We describe a case of supernumerary phantom limb following focal cerebral ischaemia and discuss its neuropsychological, neurophysiopathological and neuroradiological features in light of previous data in the literature. The illusory perception of a phantom limb, seldom reported as a consequence of cerebral lesions, seems in this case to be due to the right subcortical damage altering sensory input to the higher somatosensory cortical areas involved in body image.

We have assessed 26 aphasic patients, matched in pairs as closely as possible for personal data (age, sex, education), neurological damage suffered (nature, site and size of lesions) and characteristics of linguistic impairments (type of aphasic syndrome and severity of aphasia). These patients were therefore distinguishable only by the presence (n=13) or absence (n=13) of structured, systematic language therapy. The assignment to one group or the other was not random; rather, the patients who constitute the non-rehabilitated group could not, for logistic and/or familial reasons, attend language therapy sessions. Our findings confirm the effectiveness of language rehabilitation in aphasic disorders: at the end of 6 months of therapy the number of patients who met our criterion for improvement was significantly higher in the treated group in the expressive language modality. The rehabilitated and non-rehabilitated groups did not differ significantly at 4 months post-onset, while they did differ significantly at 7 months post-onset; this shows that the duration of treatment seems to be a determining factor in the effectiveness of language rehabilitation.

The effects of a prestimulus on the electrically elicited blink reflex components were investigated in 20 healthy subjects. In the first group of 10 subjects (warned group), electric shocks were delivered in isolation or preceded, at an interstimulus interval (ISI) of 0.1 s, 1 s, or 10 s, by a visual or acoustic warning stimulus. In the second group of 10 subjects (unwarned group), the electric shocks were delivered either in isolation or preceded, at the same ISI, by visual or acoustic stimuli having no warning value. The modulation of the three blink reflex components was then analysed. Compared to the baseline condition, the R1 oligosynaptic component was enhanced at 0.1 s and 1 s ISI, in the warned group with the visual prestimulus, but only at 0.1 s after a visual and acoustic prestimulus in the unwarned group. On the contrary, the polysynaptic responses showed a different course: R2 was significantly reduced at the 0.1 s interval in the warned group with both the prestimuli, and only with the visual prestimulus in the unwarned group. The R3 was inhibited at all three intervals with the visual prestimulus, and at the 0.1 s and 1 s with the acoustic one in the warned group, and only at 0.1 s in the unwarned group, both after visual and acoustic prestimuli. The decrement in R2 and R3 observed with the shortest interval was probably related to the prepulse inhibition of startle reflex. Furthermore, only R3 was still inhibited at longer intervals, when the sustained processes of attention may have influenced this component. Perhaps this combination of events represents, in the warned group, the best preparation for voluntary reflex reaction.

We describe the case of a 56 year old female, with a history of migraine since adolescence, who experienced two episodes of transient topographical disorientation in the absence of intellectual deterioration or evident focal cerebral lesions.

Fr6goli delusion and erotomaniaThe Fregoli delusion involves the belief that a familiar person disguises himself or herself as others.It was named after an Italian on July 12,

The relatively few studies concerning spontaneous recovery from aphasia yield contradictory findings because of the large number of influencing factors. We have assessed a selected sample of 45 patients, none of whom received language therapy, in order to determine such patients' chances of spontaneous recovery in relation to type and severity of aphasia and size of lesion. Our results show comprehension to have the best recovery, independent of type and severity of aphasia. Expression shows a lower recovery, especially for non-fluent aphasics; their performance is also negatively influenced by oral apraxia. In addition, the overall severity of aphasia, associated with large lesions, is a negative prognostic factor for recovery of expression.

The sensitivity of the Mini-Mental State Examination (MMSE) was assessed in a sample of patients with dementia of the Alzheimer type or vascular dementia. The MMSE identified the majority of pts with diffuse cognitive impairment but did not discriminate between the two types of dementia. It failed to detect mild deterioration or forms in which only some cognitive functions were impaired. The test is therefore not sufficient for distinguishing deteriorated from non deteriorated, pts, although it is still useful in mass screening or for a quick assessment of deterioration in the course of clinical neurological examination.

A striking dissociation between the inability to identify living things plus food, along with a preserved ability to identify inanimate objects has been observed in patients who are recovering from herpes simplex encephalitis. In order to find out if a similar dissociation is also present in Alzheimer's disease (where the suspected initial site of parenchymal atrophy involves the same areas affected by herpes simplex virus), we carried out five experimental linguistic tasks to compare Alzheimer's patients' performance therein with that of vascular dementia patients and controls. Our results indicate a constant parallel between the category-specific semantic impairment of Alzheimer's patients and that described in patients recovering from herpes simplex encephalitis. The dissociation of living things+food vs inanimate objects in Alzheimer's disease appears to be of diagnostic value: it is not present in vascular dementia.