We performed a multicenter survey using a semistructured interview in 1,072 consecutive patients with Parkinson's disease (PD) enrolled during 12 months in 55 Italian centers to assess the prevalence of nonmotor symptoms (NMSs), their association with cognitive impairment, and the impact on patients' quality of life (QoL). We found that 98.6% of patients with PD reported the presence of NMSs. The most common were as follows: fatigue (58%), anxiety (56%), leg pain (38%), insomnia (37%), urgency and nocturia (35%), drooling of saliva and difficulties in maintaining concentration (31%). The mean number of NMS per patient was 7.8 (range, 0-32). NMS in the psychiatric domain were the most frequent (67%). Frequency of NMS increased along with the disease duration and severity. Patients with cognitive impairment reported more frequently apathy, attention/memory deficit, and psychiatric symptoms. Apathy was the symptom associated with worse PDQ-39 score but also presence of fatigue, attention/memory, and psychiatric symptoms had a negative impact on QoL. These findings further support a key role for NMS in the clinical frame of PD and the need to address them specifically in clinical trials using dedicated scales.

The PRIAMO study is a cross-sectional longitudinal observational study aimed at describing epidemiology and evolution of non-motor symptoms (NMS) in patients with different forms of parkinsonism recruited in 55 Italian centres and evaluated over 24 months. In this paper, we are reporting prevalence and clinical characteristics of NMS in patients with atypical and secondary parkinsonism. Out of 1307 consecutive patients with a diagnosis of parkinsonism, 83 patients had vascular parkinsonism (VP), 34 had multiple system atrophy (MSA), 30 had progressive supranuclear palsy (PSP), 14 had dementia with Lewy bodies (DLB) and 11 had corticobasal degeneration (CBD). MSA and DLB had the highest number of NMS domains and symptoms, respectively. Gastrointestinal symptoms, pain, urinary problems and postural instability due to orthostatic hypotension were most frequent in MSA. Sleep disturbances were also common with a prevalence of approximately 70% in all diagnostic groups but CBD (36%). Psychiatric symptoms and attention and memory impairment were frequently observed in all diagnoses but were most prevalent among DLB patients, whereas the prevalence of skin and respiratory disorders was rather low in all forms, ranging between 10 and 30%. Atypical parkinsonism patients also reported a low QoL, with no significant differences among the different forms, whereas PD and VP patients had a better QoL.

Non-motor symptoms are gaining relevance in Parkinson's disease (PD) management but little is known about their progression and contribution to deterioration of quality of life. We followed prospectively 707 PD patients (62 % males) for 2 years. We assessed non-motor symptoms referred to 12 different domains, each including 1-10 specific symptoms, as well as motor state (UPDRS), general cognition, and life quality. Hoehn & Yahr (H&Y) stage was used to categorize patient status (I-II mild; III moderate; IV-V severe). We found that individual non-motor symptoms had variable evolution over the 2-year follow-up with sleep, gastrointestinal, attention/memory and skin disturbances (hyperhidrosis and seborrhea) becoming more prevalent and psychiatric, cardiovascular, and respiratory disorders becoming less prevalent. Development of symptoms in the cardiovascular, apathy, urinary, psychiatric, and fatigue domains was associated with significant life-quality worsening (p < 0.0045, alpha with Bonferroni correction). During the observation period, 123 patients (17 %) worsened clinically while 584 were rated as stable. There was a fivefold greater increase in UPDRS motor score in worse compared with stable patients over 24 months (p < 0.0001 vs. baseline both in stable and worse group). The total number of reported non-motor symptoms increased over 24 months in patients with motor worsening compared to stable ones (p < 0.001). Thirty-nine patients died (3.4 % of patients evaluable at baseline) with mean age at death of 74 years. Deceased patients were older, had significantly higher H&Y stage and motor score, and reported a greater number of non-motor symptoms at baseline. In conclusion, overall non-motor symptom progression does not follow motor deterioration, is symptom-specific, and only development of specific domains negatively impacts quality of life. These results have consequences for drug studies targeting non-motor features.

We assessed the occurrence of neurological signs and symptoms in adult patients with celiac disease and evaluated the correlation between neurological features and diet. A total of 176 patients and 52 age-matched controls underwent a semistructural interview and a neurologic examination. The effect of gluten-free diet was evaluated by comparing the prevalence of signs and symptoms among patients adhering to a gluten-free diet and patients on an unrestricted diet. The occurrence of headache, dysthymia and signs of peripheral neuropathy was significantly higher in patients with celiac disease than in control subjects. Adherence to a strict gluten-free diet was associated with a significant reduction of headache, dysthymia, cramps and weakness, but did not modify the occurrence of paresthesia or hyporeflexia. Neurological signs and symptoms are associated with celiac disease and can be ameliorated by a gluten-free diet.

Based on recent data about the association between restless legs syndrome (RLS) and migraine, we performed an observational study on the occurrence of RLS in patients affected by primary headaches. Two hundred headache patients (149 women and 51 men) and 120 (90 women and 30 men) sex-and age-matched control subjects were included. In the headache group, migraine without aura (MO) was the most represented headache type (n=114), followed by the "mixed" group (n=40) with MO, migraine with aura (MA) and frequent episodic tension-type headache (ETTH) in various combinations, and by ETTH alone (n=22). The remaining patients suffered from MA alone (n=10 MA), episodic cluster headache (ECH n=12) and primary stabbing headache (n=2). RLS frequency was significantly higher in headache patients than in control subjects (22.4% vs. 8.3, p=0.002) independently of sex, although with a female preponderance (84%) in both groups. More than 60% (n=27) of RLS patients were affected by MO and 30% (n=13) by a combination of two headache types (p> or =0.001), with a very low frequency of RLS for the other types of headache. No RLS patient had ECH. No statistical differences were observed among clinical characteristics of different types of headache in groups with and without RLS. In both headache and control groups, higher scores for depression and anxiety were more frequent in subjects with RLS compared with those without RLS. Furthermore, headache patients with RLS reported sleep disturbances more frequently compared to those without RLS (50.0% vs. 32.7%; p<0.0001) and showed a normal or underweight body mass index. Our data seem to confirm the existence of an association between RLS and primary headaches, particularly with migraine, as already demonstrated. The absence of RLS in ECH patients is very interesting. Many pathogenetic considerations about links between RLS and primary headaches could be given, the most fitting involving dopamine and melatonin.