Idiopathic cervical dystonia and non-motor symptoms: a pilot case-control study on autonomic nervous system.

PURPOSE: Non-motor symptoms, such as sleep disturbances, fatigue, neuropsychiatric manifestations, cognitive impairment, and sensory abnormalities, have been widely reported in patients with idiopathic cervical dystonia (ICD). This study aimed to clarify the autonomic nervous system (ANS) involvement in ICD patients, which is still unclear in the literature. METHODS: We conducted a pilot case-control study to investigate ANS in twenty ICD patients and twenty age-sex-matched controls. The Composite Autonomic System Scale 31 was used for ANS clinical assessment. The laser Doppler flowmetry quantitative spectral analysis, applied to the skin and recorded from indices, was used to measure at rest, after a parasympathetic activation (six deep breathing) and two sympathetic stimuli (isometric handgrip and mental calculation), the power of high-frequency and low-frequency oscillations, and the low-frequency/high-frequency ratio. RESULTS: ICD patients manifested higher clinical dysautonomic symptoms than controls (p < 0.05). At rest, a lower high-frequency power band was detected among ICD patients than controls, reaching a statistically significant difference in the age group of ≥ 57-year-olds (p < 0.05). In the latter age group, ICD patients showed a lower low-frequency/high-frequency ratio than controls at rest (p < 0.05) and after mental calculation (p < 0.05). Regardless of age, during handgrip, ICD patients showed (i) lower low-frequency/high-frequency ratio (p < 0.05), (ii) similar increase of the low-frequency oscillatory component compared to controls, and (iii) stable high-frequency oscillatory component, which conversely decreased in controls. No differences between the two groups were detected during deep breathing. CONCLUSION: ICD patients showed ANS dysfunction at clinical and neurophysiological levels, reflecting an abnormal parasympathetic-sympathetic interaction likely related to abnormal neck posture and neurotransmitter alterations.

Electrophysiological and neuropsychological assessment of cognition in spinocerebellar ataxia type 1 patients: a pilot study.

BACKGROUND: Event-related potentials (ERPs) reflect cognitive processing: negative early components (N100, N200) are involved in the sensory and perceptual processing of a stimulus, whereas late positive component P300 requires conscious attention. Both neuropsychological and affective disorders are present in patients with spinocerebellar ataxia type 1 (SCA1), but the underlying mechanisms need further clarification. MATERIALS AND METHODS: In this pilot study, we assessed cognitive processing by recording auditory ERPs in 16 consecutive SCA1 patients and 16 healthy controls (HC) matched for age and sex. Motor and nonmotor symptoms were evaluated using the Scale for the Assessment and Rating of Ataxia (SARA) and an extensive neuropsychological battery. ERPs were recorded using an oddball paradigm, and peak latency and amplitude of N100, N200, and P300 were measured in the averaged responses to target tones. RESULTS: We found in SCA1 significantly increased latencies of N200 and P300 (p=0.033, p=0.007) and decreased amplitudes of N100 and P300 (p=0.024, p=0.038) compared with HC. Furthermore, P300 latency had the highest AUC in the discrimination of SCA1 in ROC analysis. The expansion of trinucleotide repeats correlated with P300 latency (r=-0.607, p=0.048), whereas both P300 and N100 amplitudes correlated with the severity of motor symptoms (r=-0.692, p=0.003; r=-0.621; p=0.010). Significant correlations between P300 latency and the scores of Emotion Attribution Task (r=-0.633, p=0.027), as well as between N200 latency and the scores of Frontal Assessment Battery and Stroop test (r=-0.520, p=0.047; r=0.538, p=0.039), were observed. CONCLUSIONS: This research provides for the first time an extensive characterization of ERPs as useful electrophysiological markers to identify early cognitive dysfunction in SCA1.

The Incidence of Myasthenia Gravis in the Province of Ferrara, Italy, in the Period of 2008-2022: An Update on a 40-Year Observation and the Influence of the COVID-19 Pandemic.

Myasthenia gravis (MG) is the most common neuromuscular junction disorder. We evaluated the MG incidence rate in the province of Ferrara, Northern Italy, over two time frames (2008-2018 and 2019-2022, i.e., the COVID-19 pandemic) and considered early-onset (EOMG), late-onset (LOMG), and thymoma- and non-thymoma-associated MG. Moreover, in the second period, we assessed its possible relationship with SARS-CoV-2 infection or COVID-19 vaccination. We used a complete enumeration approach to estimate the MG incidence and its temporal trend. For the period of 2008-18, 106 new cases were identified (mean incidence rate 2.7/100,000 people). The highest rates were observed for the over-70 age group and in rural areas, with 17% of thymoma-associated MG. During the COVID-19 period, 29 new cases were identified (average incidence rate 2.1/100,000 people), showing a marked (though not statistically significant) decrease in the mean annual incidence compared to the previous period. Again, the highest rate was observed for the over-70 age group. The first period was in line with our previous observations for the period between 1985 and 2007, highlighting a rising incidence of LOMG and a marked decrease in EOMG. During the COVID-19 period, incidence rates were lower in the first years whereas, when the pandemic ended, the previous trend was confirmed.

Acute respiratory failure onset in a patient with Guillain-Barré syndrome after Legionella-associated pneumonia: a case report.

A 69-year-old white man was admitted because of a clinical history of persistent cough and fever. Chest x-rays showed bilateral lung infiltrates with air bronchograms, whereas the urine antigen test resulted positive for Legionella pneumophila. The next day, he was transferred to the intensive care unit and intubated because of severe renal and respiratory distress. Neurological examination revealed distal weakness and loss of deep tendon reflexes in lower extremities. Nerve conduction studies displayed severe demyelinating sensorimotor polyneuropathy, and plasmapheresis was therefore applied with mild improvement. Few weeks after, dysphagia occurred and electrophysiologic tests showed progressive axonal involvement with spread of demyelination to the cranial nerves. The patient underwent a new plasmapheresis course and slowly reached stable clinical improvement of neurological status, which allowed him to be safely discharged. This case showed a critical onset with respiratory failure and kidney functional impairment due to L. pneumophila, subsequently disclosing Guillain-Barré syndrome.

Migraine-like headache with autonomic symptoms in midbrain malformation.

We report a case of midbrain malformation characterized by right deviation of the medulla oblongata associated with elongation and ectasia of the basilar and left vertebral arteries in a patient with a long history of migraine-like headache with autonomic symptoms.

Posterior reversible encephalopathy syndrome in an 87-year-old woman with Escherichia coli bloodstream infection.

We present the case of an 87-year-old woman with history of hypertension, hypercholesterolemia, ischemic heart diseases, urinary tract infections, and cerebrovascular disease who experienced a transient clinical picture characterized by confusion, lethargy, and acute renal dysfunction in the course of urinary tract infection with Escherichia coli bacteremia. Escherichia coli bloodstream infection was associated with brain computed tomography (CT) and magnetic resonance imaging (MRI) patterns in which the lesion distribution was consistent with posterior reversible encephalopathy syndrome (PRES). Diagnosis of PRES was confirmed by demonstration of vasogenic edema on apparent diffusion coefficient (ADC) maps and near-complete resolution of clinical manifestations at discharge.

Migraine.

Migraine is a neurovascular disorder which affects one fifth of the general population. Disability due to migraine is severe and involves patients from infancy through senescence and it is aggravated by the fact there is no complete cure. However, various drugs for the symptomatic or prophylactic treatment of the disease are available. Recently, better knowledge of the neurobiological and pharmacological aspects of a subset of trigeminal primary sensory neurons has provided key information for the development of effective molecules that specifically target the activation of the trigeminovascular system and may represent a significant advancement in the treatment of the disease. These novel antagonists block the receptor for the sensory neuropeptide calcitonin gene-related peptide (CGRP), which upon release from peripheral terminals of trigeminal perivascular neurons dilates cranial arterial vessels. Whether neurogenic vasodilatation is the major contributing factor to generate the pain and the associated symptoms of the migraine attack or whether other sites of action of CGRP receptor antagonists are responsible for the antimigraine effect of these compounds is the subject of current and intense research.

Pallidal stimulation for segmental dystonia: long term follow up of 11 consecutive patients.

Pallidal stimulation is a convincing and valid alternative for primary generalized dystonia refractory to medical therapy or botulinum toxin. However, the clinical outcome reported in literature is variable most likely because of heterogeneity DBS techniques employed and /or to clinical dystonic pattern of the patients who undergo surgery. In this study, we report the long term follow up of a homogeneous group of eleven subjects affected by segmental dystonia who were treated with bilateral stimulation of the Globus Pallidus pars interna (GPi) from the years 2000 to 2008. All the patients were evaluated, before surgery and at 6-12-24-36 months after the treatment, in accordance with the Burke Fahn Marsden Dystonia Rating Scale (BFMDRS). Our study indicates that DBS promotes an early and significant improvement at 6 months with an even and a better outcome later on. The analysis of specific sub items of the BFMDRS revealed an earlier and striking benefit not only as far as segmental motor function of the limbs but also for the complex cranial functions like face, (eyes and mouth), speech and swallowing, differently from results reported in primary generalized dystonia. Deep Brain Stimulation of GPi should be considered a valid indication for both generalized and segmental dystonia when other therapies appear ineffective.

CGRP receptors in the control of pain and inflammation.

Calcitonin gene related peptide (CGRP) has been proposed to contribute to pain transmission and inflammation and for these reasons to the mechanism of migraine. CGRP is, in fact, expressed in and released from a subset of polymodal primary sensory neurons of the trigeminal ganglion. Release of CGRP in the dorsal spinal cord has been associated to nociceptive transmission, and release from perivascular nerve endings causes neurogenic vasodilatation. CGRP levels increase in the cranial circulation during migraine attacks, and GRP injection in migraineurs results in migraine-like attacks. Most importantly, two chemically unrelated CGRP-receptor antagonists, the parenteral agent, olcegepant, and the orally available telcagepant demonstrated efficacy in the treatment of migraine attacks, thus supporting CGRP as an important mediator in migraine.

Botulinum toxin type A reduces capsaicin-evoked pain and neurogenic vasodilatation in human skin.

The effect of Botulinum Toxin type A (BoNT/A) on pain and neurogenic vasodilatation induced by application to the human skin of thermal stimuli and capsaicin was evaluated in a double blind study. A capsaicin cream (0.5 ml of a 0.075%) was applied to the skin of both forearms of eighteen subjects randomly pretreated with either BoNT/A (Botox) or 0.9% saline (NS). Capsaicin was applied to a skin area either inside (protocol A) or adjacent to the BoNT/A treated area (protocol B). Pre-treatment with BoNT/A did not affect thermal-specific and thermal-pain thresholds (by quantitative sensory testing). However, capsaicin-induced pain sensation (by a visual analogue scale), flare area (by acetate sheet) and changes in cutaneous blood flow (CBF, by laser Doppler flowmetry) were reduced when capsaicin was administered inside (protocol A) the BoNT/A treated area. In Protocol B, capsaicin-induced pain was unchanged, and capsaicin-induced flare/increase in CBF were reduced only in the area treated with BoNT/A, but not in the BoNT/A untreated area. Results indicate that (i) BoNT/A reduces capsaicin-induced pain and neurogenic vasodilatation without affecting the transmission of thermal and thermal-pain modalities; (ii) reduction in capsaicin-induced pain occurs only if capsaicin is administered into the BoNT/A pretreated area; (iii) reduction in neurogenic vasodilatation by BoNT/A does not contribute to its analgesic action. BoNT/A could be tested for the treatment of conditions characterised by neurogenic inflammation and inflammatory pain.

CGRP and migraine: neurogenic inflammation revisited.

For more than a century neurogenic inflammation has been proposed to have a role in various human diseases. The present review will cover the conceptual steps of the itinerary that has led to the conclusion that neurogenic inflammation is important in migraine. Of particular relevance for the object of this article is the observation that tachykin-independent neurogenic inflammatory responses are evident in rodents, but much less pronounced or absent in other mammal species, including man, whereas neurogenic vasodilatation, most likely mediated by CGRP, occurs in most mammalian species and also in man. Recent evidence that a CGRP receptor antagonist was effective in the treatment of migraine attack supports the hypothesis that neurogenic vasodilatation is a major underlying mechanism of migraine.

Is there a decrease in Guillain-Barré syndrome incidence after bovine ganglioside withdrawal in Italy? A population-based study in the Local Health District of Ferrara, Italy.

There have been many reports of cases of Guillain-Barré syndrome (GBS) after therapeutic injection of bovine ganglioside preparations with the result that they were withdrawn in Italy in December 1993. As the relationship between bovine gangliosides and GBS has not yet been established, a further epidemiological investigation in the Local Health District (LHD) of Ferrara, Italy, was carried out in the years 1994-2001 to verify whether the incidence of GBS had changed after ganglioside withdrawal. The other aim of this investigation was to update the incidence of GBS in this area since the two previous investigations we carried out showed an increase in incidence from the years 1981-1987 to the years 1988-1993. The cases of GBS were identified prospectively. To guarantee completeness of case ascertainment, an intensive retrospective survey of all possible sources of cases for the entire study period was performed. The mean annual crude incidence rate in the years 1994-2001 (based on 26 new cases) was 1.97 per 100,000 population (95% CI 1.29-2.89), whereas it had been 1.87 per 100,000 population (95% CI 1.35-2.52) in the years 1981-1993 (based on 43 cases) when gangliosides were available. The age-adjusted rates were almost identical (1.66 and 1.65 per 100,000 population, respectively). Although ganglioside administration could have triggered, on the basis of an individual susceptibility, an immunologic reaction which produced GBS, the incidence of GBS in the study area did not change after ganglioside withdrawal. In the whole period 1981-2001, a temporal pattern of incidence was reported with an increase towards a peak in 1990-1992 and a progressive decline thereafter. This temporal pattern did not seem related to ganglioside withdrawal, and no definite explanation for it was found which could imply that the disease incidence is less stable than it was deemed.

Incidence of amyotrophic lateral sclerosis in the local health district of Ferrara, Italy, 1964-1998.

One of the epidemiologic characteristics of amyotrophic lateral sclerosis (ALS) still under discussion is whether the incidence of ALS is increasing over time. We performed a new investigation expanding our previous study of ALS in the local health district (LHD) of Ferrara, northern Italy, to determine whether there have been any changes in the incidence of ALS in the years 1964-1998. We used a complete enumeration approach by reviewing all possible sources of case collection available in the study area. We selected all patients with definite and probable ALS according to the World Federation of Neurology criteria. The mean annual crude incidence rate for 1964-1998 was 1.63 per 100,000 population (95% CI 1.31-2.00). An increase in incidence from 1.07 to 2.19 per 100,000 population was observed during the study period. It was greater in women and in individuals of 70 years old and over. Substantial population ageing occurred in the LHD of Ferrara during the study period and it was more prominent in women. This increase in incidence seems to be explained mainly by the ageing of the population. Moreover, greater precision in diagnosis of ALS in elderly women, rather than better case ascertainment of diagnosed patients, may have contributed to the increase. The role of environmental factors cannot be excluded, but based on the present findings, it seems to be of little importance.

Upper and lower face and ideomotor apraxia in patients with Alzheimer's disease.

INTRODUCTION: Apraxia of face movement in Alzheimer's disease (AD) has been rarely investigated. This study aimed at investigating the frequency of lower (mouth, tongue and throat) and upper (eyes and eyebrows) face apraxia, in AD and its relationship with limb apraxia and severity of dementia. METHODS: Fifty seven patients with AD were tested with a new standardised test of face apraxia including upper and lower face movements, which uses an item-difficulty weighted scoring procedure, the IMA test, a test of ideomotor apraxia and the M.O.D.A., a means to assess dementia severity. RESULTS: Thirteen (23%) and 19 (33%) participants were below cut-off respectively on the upper and lower face apraxia test. Both sections of the Face Apraxia Test correlated significantly with the Ideomotor Apraxia Test. However, double dissociations between different types of apraxia were observed. Both the upper and lower face apraxia tests correlated significantly with the measure of dementia severity. CONCLUSIONS: The finding show that a proportion of AD patients fails face apraxia tests. Their face apraxia is interlinked with ideomotor limb apraxia, although dissociations are possible. Severity of dementia deterioration accounts for a good proportion of the variability of AD patients' performance on face apraxia tests.