Clinical and genetic findings in a series of Italian children with pure hereditary spastic paraplegia.

BACKGROUND: hereditary spastic paraplegias (HSP) are a group of neurodegenerative disorders characterized by progressive lower extremity spastic weakness. SPG7, SPG4 and SPG3A are some of the autosomal genes recently found as mutated in recessive or dominant forms of HSP in childhood. SPG31 is more often associated with a pure spastic paraplegia phenotype, but genotype-phenotype correlation is still unclear. The aims of the current study was: (i) to verify the mutational frequency of SPG4, SPG3A, SPG31 and SPG7 genes in our very-well-selected childhood sample, and (ii) to improve our knowledge about the clinical and electrophysiological HSP phenotypes and their possible correlation with a specific mutation. METHODS: a sample of 14 Italian children affected by pure HSP (mean age at diagnosis 5.9 years) was extensively investigated with electrophysiological, neuroradiological and genetic tests. RESULTS: three SPG4 mutations were identified in three patients: two novel missense mutations, both sporadic, and one multiexonic deletion already reported. A novel large deletion in SPG31 gene involving exons 2-5 was also detected in one young patient. No mutations in the SPG7 and in the SPG3A genes were found. CONCLUSIONS: our data confirm that HSP represent a heterogeneous group of genetic neurodegenerative disorders, also in sporadic or autosomal recessive early onset forms. Multiplex Ligation-dependent Probe Amplification-based mutation screening for SPG4 and SPG31 genes would be added to sequencing-based screening of SPG4, SPG31 and SPG3A genes in the routine diagnosis of HSP children.

Dysfunction of the magnocellular stream in Alzheimer's disease evaluated by pattern electroretinograms and visual evoked potentials.

BACKGROUND: Visuo-spatial disturbances could represent a clinical feature of early stage Alzheimer's disease (AD). The magnocellular (M) pathway has anatomo-physiological characteristic which make it more suitable for detecting form, motion and depth compared with parvocellular one (P). OBJECTIVE: Aim of our study was to evaluate specific visual subsystem involvement in a group of AD patients, recording isoluminant chromatic and luminance pattern electroretinograms and pattern visual evoked potentials. MATERIAL AND METHODS: data were obtained from 15 AD patients (9 females and 6 males, mean age+/-1SD: 77.6+/-4.01 years) not yet undergoing any treatment, and from 10 age-matched healthy controls. Diagnosis of probable AD was clinically and neuroradiologically established. PERGs were recorded monocularly in response to equiluminant red-green (R-G), blue-yellow (B-Y) and luminance yellow-black (Y-Bk) horizontal square gratings of 0.3c/deg and 90% contrast, reversed at 1Hz. VEPs were recorded in response to full-field (14 deg) equiluminant chromatic R-G, B-Y and luminance Y-Bk sinusoidal gratings of 2c/deg, presented in onset (300ms)-offset (700ms) mode, at the contrast levels of 90%. RESULTS: All data were retrieved in terms of peak-amplitude and latency and assessed using the Student's t-test for paired data. Temporal differences of PERGs and VEPs, evoked by Y-Bk grating in AD patients compared with controls, suggest a specific impairment of the magnocellular stream. CONCLUSIONS: Our study support the hypothesis that the impairment of the PERGs and VEPs arising from the magnocellular streams of visual processing may indicate a primary dysfunction of the M-pathways in AD.

Sleep disturbances in elderly subjects: an epidemiological survey in an Italian district.

OBJECTIVES: Disturbed sleep is common in elderly people and has been related to comorbidities. The aim of this study was to evaluate the prevalence of sleep problems and their relationship with chronic disease in an elderly population. MATERIALS AND METHODS: The whole population of subjects aged more than 65 years, in the municipality of Vecchiano, Pisa was considered as eligible and underwent a clinical interview and a questionnaire about insomnia, sleepiness, snoring and sleep apnea. A model of logistic regression was applied to the data. RESULTS: The participation rate was 60.3% (1427 subjects). Insomnia was observed in 44.2% of our population, while sleepiness in 31.3%, snoring in 47.2% and sleep apnea in 9.0%. The most common diseases associated with sleep symptoms were depression, cognitive decline and diabetes. CONCLUSIONS: Our results confirm that sleep problems are very common in elderly subjects and closely related to medical and psychiatric illnesses.

Transcranial magnetic stimulation mapping: a model based on spline interpolation.

Transcranial magnetic stimulation (TMS) is a non-invasive method to investigate motor pathways and to create a map of the somatotopical organization of the motor cortex: ordinary mapping procedures requires a focal brain stimulation over different spots of the scalp and electromyographic (EMG) recording from a muscle. Finding an appropriate and a valid visual representation of collected data is a crucial step in research and clinical field to allow a relatively fast, intra- and inter-patient comparison of motor cortex mapping. Aim of this study was to develop and to validate a method to map cortical representation of an intrinsic hand muscle (abductor digiti minimi, ADM) using a two-dimensional spline interpolation of EMG peak amplitudes obtained with TMS. The interpolated model will result in a graphical colour-scaled representation of the motor cortex for the investigated muscle; fitted model was finally validated by comparing derived parameters with those directly measured to ensure the strength and reliability of the model. Ten healthy volunteers (mean age+/-S.D.: 35.3+/-4.7 years, 4 males and 6 females) were enrolled in the study. Transcranial stimulation was performed by placing a figure-of-eight coil over a predefined grid on the scalp of the subject. EMG responses were recorded from the right abductor digiti minimi (ADM): averaged EMG peak amplitudes obtained at each node were then used to perform spline interpolation and to derive other parameters like center of gravity (CoG). Arithmetical mean of all resting motor threshold at the hotspot was 50.6+/-3.4% of the maximal stimulator output. Average amplitude at the hotspot was 1.72+/-0.80 mV and its coordinates, expressed as median, were x=4.5 cm and y=0.0 cm. Mean CoG was located at x=4.86+/-0.57 cm and y=0.35+/-0.10 cm. Mean interpolated peak coordinates for ADM were xf=4.86+/-0.58 cm and yf=0.36+/-0.12 cm, while mean fitted peak amplitude was 0.87+/-0.47 mV. Results suggest how it is possible to map the primary motor cortex using two-dimensional spline interpolation of peak-to-peak amplitudes obtained by single pulse TMS delivered on several scalp positions, which will result in a smooth, easy to read, colour-scaled map. However, like other visual representation modalities, the interpolation should become complementary to traditional methods and not a substitute of a precise and accurate cortical motor mapping.

CSF phosporylated TAU protein levels correlate with cerebral glucose metabolism assessed with PET in Alzheimer's disease.

One major goal of drug development would be the establishment of biomarkers as objective indicators of normal biological and pathogenetic processes, or pharmacological response to a therapeutic intervention. A potential approach is to investigate proteins in CSF linked to key neuropathological features of Alzheimer's disease (AD). Recently CSF phosphorylated-Tau (p-Tau) levels have been reported to reflect neurofibrillary changes within the brain of patients with AD, however the use of serial CSF investigations in order to monitor the disease progression is not applicable. PET with FDG reveals characteristic patterns in AD patients, however so far no correlation between in vivo metabolic information and pathological features has been reported. In the present study, we tested whether CSF Tau levels correlate with metabolic rate for glucose consumption in a cohort of 28 AD patients. We found a statistically significative correlation between both CSF total and p-TAU protein and relative metabolic indexes obtained from 18FDG-PET scans in parietal, temporal and occipital lobes bilaterally. These results indicate the existence of a correlation between impairment of cerebral metabolism, estimated throughout FDG-PET, and CSF Tau protein levels.

A low-cost interface for control of computer functions by means of eye movements.

Human-computer interactions (HCI) have become an important area of research and development in computer science and psychology. Appropriate use of computers could be of primary importance for communication and education of those subjects which could not move, speak, see or hear properly. The aim of our study was to develop a reliable, low-cost and easy-to-use HCI based on electrooculography signal analysis, to allow physically impaired patients to control a computer as assisted communication. Twenty healthy subjects served as volunteers: eye movements were captured by means of four electrodes and a two-channel amplifier. The output signal was then transmitted to an "Analog to Digital" (AD) converter, which digitized the signal of the amplifier at a rate of 500 Hz, before being sent to a laptop. We designed and coded a specific software, which analyzed the input signal to give an interpretation of eye movements. By means of a single ocular movement (up, down, left and right) the subjects were then able to move a cursor over a screen keyboard, passing from one letter to another; a double eye blink was then necessary to select and write the active letter. After a brief training session, all the subjects were able to confidently control the cursor and write words using only ocular movements and blinking. For each subject we presented three series of randomized words: mean time required to enter a single character was about 8.5s, while input errors were very limited (less than 1 per 250 characters). Our results confirm those obtained in previous studies: eye-movement interface can be used to properly control computer functions and to assist communication of movement-impaired patients.

Mismatch negativity analysis in drug-resistant epileptic patients implanted with vagus nerve stimulator.

It is well known that some epileptic patients does not respond to conventional treatments, despite multiple combination of antiepileptic drugs, and they are therefore considered drug-resistant. For these patients, vagal nerve stimulation (VNS) represents a successful alternative to traditional therapy, and it is generally well tolerated; beside benefits on seizure frequency, VNS showed positive effects on cognition and mood. Aim of this study was to investigate short-term memory changes in a group of 12 patients implanted with VNS, through Mismatch Negativity wave (MMN). After 1 year of follow-up, MMN latencies and amplitudes did not show significant changes following VNS implantation, independently on current intensity, as compared with pre-implantation values. In two patients, MMN values, which were abnormal before VNS implantation, showed a major reduction in latency and an increase in amplitude after implantation, suggesting a likely positive effect of VNS on pre-attentive processes investigated by MMN.

Quantitative EEG analysis in post-traumatic anosmia.

Many objective and quantitative methods have been developed to create a procedure or a device to prove, describe and quantify olfactory deficit and anosmia, especially after a head trauma. Electrophysiological testing throughout olfactoelectroencephalography (olfactoEEG) is based on brain activity desynchronisation, and on the subsequent disappearance of alpha activity on the posterior regions after an olfactory stimulus. Yet traditional evaluation of EEG can be difficult, because of little or hardly detectable alpha activity on the posterior regions ('alpha rare'). The aim of this study was to evaluate the Olfactory Stop Reaction (OSR) by means of frequency band power calculation and subsequent topographical mapping in patients with post-traumatic anosmia, who presented 'alpha rare' EEG. Twenty-five consecutive patients, affected by anosmia caused by head trauma, were submitted to an EEG recording with olfactory stimulation. After signal processing and analysis, an Olfactory Stop Reaction was detected in 17 out of 25 patients; moreover, in these patients we detected a significant decrease in alpha band power in the occipital regions and an increase in theta band power on midline frontal and central regions after olfactory stimulation. In the remaining eight patients, no significant variation in band power was observed. In conclusion, an objective evaluation of the olfactory function with this method of automatic EEG signal analysis allows the limits given by psychophysical methods and traditional EEG to be overcome and attempts to fulfil the requirements for standardization of olfactory function evalution.

Chromatic pattern-reversal electroretinograms (ChPERGs) are spared in multiple system atrophy compared with Parkinson's disease.

Idiopathic Parkinson's disease (IPD) patients have abnormal visual evoked potentials (VEPs) and pattern electroretinograms (PERGs), attributed to dopaminergic transmission deficiency in visual pathway, probably the retina. VEP abnormalities are not reported in multiple system atrophy (MSA). The aim of this study was to investigate and compare chromatic (Ch) red-green (R-G) and blue-yellow (B-Y), and luminance yellow-black (Y-Bk) PERGs in patients with MSA and IPD. We investigated 6 MSA patients (mean age: 62+/-7.4 years) not undergoing any pharmacological treatment, as well as 12 early IPD patients (mean age: 60.1+/-8.3 years) and 12 age-matched normal observers. ChPERGs were recorded monocularly in response to full-field equiluminant R-G, B-Y and Y-Bk horizontal gratings. In MSA only responses to R-G stimuli showed minimal insignificant changes (slight but not significant amplitude reduction without any significant latency delay); no significant abnormality was detected for B-Y and luminance Y-Bk stimuli. By contrast, in IPD all responses were reduced in amplitude and delayed in latency, above all for B-Y stimuli. Present data indicate that both chromatic and achromatic PERGs are virtually unaffected in MSA, whereas in early IPD they are clearly impaired, suggesting different pathogenic retinal mechanisms and a useful simple tool for distinguishing MSA from IPD.

Electrophysiological evidence by single fibre electromyography of neuromuscular transmission impairment in a case of Miller Fisher syndrome.

Miller Fisher syndrome is an autoimmune neuropathy characterised by ataxia, areflexia and ophthalmoplegia, with minimal if any limb weakness, and in the majority of cases by high titres of IgG anti-GQ1b ganglioside antibodies. In vitro electrophysiological experiments have demonstrated that these antibodies induce a transmission blockade at neuromuscular junction either pre- or post-synaptically. We report the case of a 63-year-old man with MFS that shows blood serum negative for anti-GQ1b but presents an impairment of neuromuscular transmission detected by single fibre electromyography. To the best of our knowledge, this represents the first case in the literature using jitter technique and suggests that other antibodies may be involved in the function of motor end plates by bindings to the synaptic membranes.