Narcolepsy is a common phenotype in HSAN IE and ADCA-DN.

We report on the extensive phenotypic characterization of five Italian patients from four unrelated families carrying dominant heterozygous DNMT1 mutations linked to two distinct autosomal dominant diseases: hereditary sensory and autonomic neuropathy with dementia and hearing loss type IE (HSAN IE) and autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN). Patients underwent genetic analysis of DNMT1 gene, neurophysiological tests investigating sleep, auditory functions and peripheral nervous system, ophthalmological studies including optical coherence tomography, lymphoscintigraphy, brain magnetic resonance and nuclear imaging, cerebrospinal fluid hypocretin-1, total tau, phosphorylated tau, amyloid-ß1-42 and 14-3-3 proteins measurement, skin, muscular and sural nerve biopsies. Exome and direct sequencing studies disclosed two different point mutations affecting exon 21 of DNMT1 gene in patients with ADCA-DN, a novel heterozygous point mutation in exon 20 in two affected HSAN IE siblings, and a trinucleotide deletion in exon 20 in the latter patient with HSAN IE. Phenotypic characterization pinpoints that ADCA-DN and HSAN IE represent two discrete clinical entities belonging to the same disease spectrum, with variable degree of overlap. Remarkably, narcolepsy with or without cataplexy with low/intermediate or normal cerebrospinal fluid hypocretin-1 is present in both diseases. The human leukocyte antigen DQB1*06:02 was absent in all patients. Other common symptoms and features observed in our cases, involving the central and peripheral nervous system, include deafness, optic neuropathy-previously not reported in HSAN IE-large and small fibres polyneuropathy and lower limbs oedema. Overall, the two syndromes share more characteristics than previously recognized and narcolepsy is common to both. HSAN IE and ADCA-DN are two extreme phenotypic manifestations of a DNMT1 methylopathy.

Complexity of motor sequences and cortical reorganization in Parkinson's disease: a functional MRI study.

Motor impairment is the most relevant clinical feature in Parkinson's disease (PD). Functional imaging studies on motor impairment in PD have revealed changes in the cortical motor circuits, with particular involvement of the fronto-striatal network. The aim of this study was to assess brain activations during the performance of three different motor exercises, characterized by progressive complexity, using a functional fMRI multiple block paradigm, in PD patients and matched control subjects. Unlike from single-task comparisons, multi-task comparisons between similar exercises allowed to analyse brain areas involved in motor complexity planning and execution. Our results showed that in the single-task comparisons the involvement of primary and secondary motor areas was observed, consistent with previous findings based on similar paradigms. Most notably, in the multi-task comparisons a greater activation of supplementary motor area and posterior parietal cortex in PD patients, compared with controls, was observed. Furthermore, PD patients, compared with controls, had a lower activation of the basal ganglia and limbic structures, presumably leading to the impairment in the higher levels of motor control, including complexity planning and execution. The findings suggest that in PD patients occur both compensatory mechanisms and loss of efficiency and provide further insight into the pathophysiological role of distinct cortical and subcortical areas in motor dysfunction.

Efficacy of thrombolytic (rt-PA) therapy in old stroke patients: the Perugia Stroke Unit experience.

The use of intravenous recombinant tissue plasminogen activator (rt-PA) administered within 3 hrs from symptom onset is beneficial in selected patients independent of age; although oldest patients (> or = 80 years) are excluded a priori. We report an experience relative to rt-PA treatment in the oldest patients including outcome at 3 months. Data were from the hospital-based Perugia Stroke Registry. Seventy-two consecutive acute stroke patients, fulfilling NINDS and EUSI-criteria were treated with rt-PA of these 23 patients (30.5%) were > or = 80 years. The median and mean age were, respectively, 72.5 and 71.1 +/- 12.7 years (range 35-94). The proportion of favorable outcome at 3-months did not differ between groups (55% elderly versus 51.1% of younger patients). Proportions of unfavorable outcome and death from baseline were similar in both groups of patients. Age did not influence prognosis in patients treated with rt-PA. The oldest stroke patients should not be excluded from rt-PA treatment on the basis of age per se.

Characteristics of delayed admission to stroke unit.

Early admission to stroke unit (SU) and factors that may cause admission delay represent relevant issues to obtain an optimal management of acute stroke. This study was aimed at recording timing from clinical onset to admission to our SU and to identify the reasons for delay. We prospectively examined acute stroke patients consecutively admitted to the Perugia SU. Baseline characteristics of stroke patients, stroke type and etiology, time from symptom onset to arrival in the SU were obtained from the Hospital-Based Perugia Stroke Registry. 60.8% of 2,213 consecutive stroke patients admitted to the SU arrived within 6 hrs and 39.2% after 6 hrs. Underestimation of symptoms was the cause of delay in 48.7% of cases. Younger age, especially for females, ischemic stroke, mild and/or unspecific symptoms and the underestimation of symptoms seem to be the main reasons for delayed arrival in the SU. To increase the proportion of stroke patients arriving in the SU within 3 hr of symptom onset, it is necessary to improve public and general practitioner awareness of stroke through educational programs.

Functional 1H-MRS findings in migraine patients with and without aura assessed interictally.

The present study was aimed at investigating changes in brain metabolites due to visual cortex activation in migraineurs and normal subjects by (1)H-magnetic resonance spectroscopy (MRS). Twenty-two migraine patients with aura, 22 migraine patients without aura, and 10 control subjects were assessed. The volume of interest (about 8 cm(3)) was placed on the visual cortex area and the visual stimulus was applied using MR-compatible goggles with a flashing red light at a frequency of 8 Hz and an intensity of 14 lx. Data were acquired over 36'40". The experimental time course was: baseline phase, from 0 to 3'40" (1 spectrum); on phase (flashing light condition), from 3'40" to 29'20" (1540") (7 spectra), and off phase, from 29'20" to the end of the experiment at 36'40" (2 spectra). The main result of photic stimulation in patients with migraine with aura is the more consistent decrease (-14.61%) of the N-acetylaspartate (NAA) signal, which is significantly greater than that found in migraine patients without aura and control subjects. A parallel slight increase in the lactate peak was also detected. The above findings support little differences in brain metabolites between the two patient groups assessed in interictal periods, which suggests a less efficient mitochondrial functioning in migraine with aura patients.