Floriano Girotti

Reduced risk factors for vascular disorders in parkinson disease patients : A case-control study

Background and Purpose— Sympathetic hyperactivity is a contributing cause of vascular disorders because it increases blood pressure, blood sugar, and blood lipids. Pervasive compromise of the central and peripheral autonomic nervous systems is common in idiopathic Parkinson disease (IPD) resulting in reduced sympathetic and parasympathetic function. We hypothesized that IPD was associated with reduced prevalence of cardiovascular disease risk factors as a result of reduced sympathetic activity. Methods— We performed a retrospective case-control study on 178 newly diagnosed consecutive IPD patients, and 533 age- (±3 years) and sex-matched controls with other neurological diseases seen over the same period at the same hospital. For each case and control the following were noted on admission: smoking, diabetes, hypertension, body mass index, serum glucose, plasma cholesterol, triglycerides and total lipid levels, and blood pressure. Results— Diabetes, history of smoking, high blood pressure, high blood glucose, high blood cholesterol, and triglycerides were significantly less frequent in IPD than controls. Conclusions— IDP is a natural model of impaired hypothalamic-pituitary-adrenal axis activity and generalized sympathetic denervation. We interpret the association of untreated IPD with reduced vascular diseases risk factors as attributable to reduced autonomic activity, suggesting that autonomic hyperactivity may be involved in the pathogenesis of vascular disorders.

Diffusion Tensor Imaging Shows Different Topographic Involvement of the Thalamus in Progressive Supranuclear Palsy and Corticobasal Degeneration

BACKGROUND AND PURPOSE: In progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), postmortem studies show different topographic involvement of the thalamus, basal ganglia, and their cortical connections. Diffusion tensor imaging (DTI) is an MR imaging technique sensitive to gray and white matter microstructure integrity. This study was performed to determine whether DTI may demonstrate microstructural differences between PSP and CBD, particularly within the thalamus and its cortical connections. MATERIALS AND METHODS: Nine patients with probable PSP, 11 with probable CBD, and 7 controls formed the study group. Apparent diffusion coefficient average (ADCave) and fractional anisotropy (FA) values were measured in regions of interest positioned in the ventrolateral (motor), medial, anterior, and posterior regions of the thalami, basal ganglia, fronto-orbital white matter, cingulum, supplementary motor area (SMA), and precentral and postcentral gyri in patients and controls. RESULTS: In PSP, ADCave values were increased in several areas: the thalamus, particularly in its anterior and medial nuclei; cingulum; motor area; and SMA. FA values were particularly decreased in the fronto-orbital white matter, anterior cingulum, and motor area. In CBD, ADCave was increased in the motor thalamus, in the precentral and postcentral gyri, ipsilateral to the affected frontoparietal cortex, and in the bilateral SMA. FA was mainly decreased in the precentral gyrus and SMA, followed by the postcentral gyrus and cingulum. CONCLUSIONS: In patients with PSP, thalamic involvement was diffuse and prevalent in its anterior part, whereas in CBD involvement was asymmetric and confined to the motor thalamus. DTI may be useful in the differential diagnosis of these 2 parkinsonian disorders.

Cause and course in a series of patients with sporadic chorea

Abstract.Objective: To identify correlations between clinical and neuroimaging features in sporadic chorea and to explicate the evolution of choreas of differing aetiologies. Methods: We analysed the clinical and neuroimaging data of 51 consecutive cases (17 males, 34 females; age 16–95 years) of sporadic chorea admitted to the neurology departments of two general hospitals from January 1994 to December 1999, and two neurological institutes from January 1997. Six months later the patients were reassessed clinically and those still with chorea (20 cases) were asked to undergo the genetic tests for Huntingtons disease and dentatorubropallidoluysian atrophy. Results: There were 9 cases of focal dyskinesias, 18 of hemichorea, and 24 of generalised chorea; onset was acute in 17, subacute in 27, and insidious in seven. Analysis permitted classification as follows: vascular-related (21 cases); vasculitis (1 case); hypoxia (2 cases); drug-induced (7 cases); AIDS-related (5 cases), borreliosis (1 case); Sydenhams chorea (1 case); hyperglycaemia (2 cases); hyponatraemia (2 cases); Huntingtons disease (HD) (5 cases) and acanthocytosis (1 case). In 3 patients neither etiological factors nor neuroradiological alterations were found. Conclusions: Although a convincing concordance between choreic signs and neuroradiological findings was possible in 4 patients only, it was possible to assign an aetiology in most cases with vascular related causes the most frequent and metabolic factors often participating. Huntingtons disease is not unusual as a cause of sporadic choreas. HIV infection is an emerging cause of chorea and AIDS-related disease should be considered in young patients presenting without a family history of movement disorders. We emphasize the importance of follow-up to identify persistent chorea for which genetic testing is mandatory.

L‐dopa long‐term treatment in Parkinson's disease Age‐related side effects

One hundred ninety L-dopa-treated parkinsonian patients have been studied according to the age at onset and to age at last examination. The frequency of major mental disturbances was significantly higher in patients older than 60 years, whereas abnormal involuntary movements and on-off phenomenon were more frequent in patients with onset before age 60. The association of normal aging and of Parkinsons disease may be responsible for the prevalence of mental disease in older patients.

Comparison of natural histories of progressive supranuclear palsy and multiple system atrophy.

Abstract. In order to identify early clinical features and survival predictors of supranuclear palsy (PSP) and multiple system atrophy (MSA), we compared the disease course of patients consecutively referred between 1987 and 1999 and followed to December 1999. Thirty-nine PSP and 74 MSA patients were diagnosed according to commonly accepted clinical criteria. Length of survival was ascertained from death certificates or by contacting relatives. Ten-year survival after disease onset was 29% for both disorders. Median survival was 7.0 years (PSP) and 7.5 (MSA). Neither age, symptoms at onset, or disability at diagnosis predicted survival. At diagnosis, all PSP patients had oculomotor palsy, whereas 89% of MSA patients had dysautonomia; bradykinesia and falls were the most frequent common signs. Distinctive early signs were palilalia, cognitive impairment and hyperreflexia in PSP; hypophonia, anterocollis and dysautonomia in MSA. MSA patients responded better to levodopa. Attention to early distinctive features can improve differential diagnosis and inform subsequent management.

Relationship between motor and cognitive disorders in Huntington's disease

SummaryAkinesia and mental decline appear to be more appropriate criteria than hyperkinesia for the evaluation of the stage and progression of Huntingtons disease (HD). In order to establish the relationship between motor and cognitive impairment in the disease, 20 non-demented HD patients were compared with 44 control subjects with respect to motor and cognitive performance. HD patients were significantly impaired in almost all cognitive functions in comparison with controls. Reaction time (RT) and movement time (MT) were considerably slower in HD patients when compared with controls and with patients with parkinsonism. Hyperkinesias did not correlate with cognitive impairment, but there was a good correlation between RT, MT and cognitive functions. Therefore, it seems that akinesia evaluated by RT and MT is an important sign in HD and proceeds at the same rate as mental decay.

Clinical and molecular studies of 73 Italian families with autosomal dominant cerebellar ataxia type I: SCA1 and SCA2 are the most common genotypes.

Abstract We clinically and genetically evaluated 73 Italian families with autosomal dominant cerebellar ataxia (ADCA) type I. Spinocerebellar ataxia (SCA) type 1 was the most common genotype (SCA1), accounting for 41% of cases (30 families), SCA2 was slightly less frequent (29%, 21 families), and the remaining families were negative for the SCA1, SCA2, and SCA3 mutations. Among the positively genotyped families, SCA1 was found most frequently in families from northern Italy (50%), while SCA2 was the most common mutation in families from the southern part of the country (56%). Slow saccades and decreased deep tendon reflexes were observed significantly more frequently in SCA2 patients, while increased deep tendon reflexes and nystagmus were more common in SCA1. In SCA1 and SCA2 families there was a significant inverse correlation between expansion size and age at onset. Analysis of triplet repeat numbers in parent-offspring pairs showed greater meiotic instability, which was associated with an earlier onset of the disease in SCA2 families than in SCA1 families.

Limb apraxia in corticobasal degeneration and progressive supranuclear palsy.

Objective: Corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) share pathologic features, and cortical and subcortical signs. Apraxia is frequently described in CBD and sometimes in PSP; however, it is difficult to distinguish ideomotor from limb-kinetic apraxia, and apraxia frequency is unclear. The authors set out to clarify the nature and frequency of apraxia in these diseases. Methods: The authors compared probable CBD and PSP patients, matched for motor disability, to healthy age-matched controls on cognitive tests and the De Renzi ideomotor apraxia test. Results: Cognitive impairment was similar, but more CBD (70.8%) than PSP (36%) patients had apraxia. CBD patients committed more apraxic errors of awkwardness and were more compromised on simple gestures; PSP patients committed more sequence errors. Conclusions: While progressive supranuclear palsy (PSP) patients had ideomotor apraxia, the peculiar gesture compromise in corticobasal degeneration (CBD) suggests that limb-kinetic apraxia is dominant. In both illnesses, the movement production system of Roy and Square appears compromised: in CBD defective control of muscle activation seems likely, producing clumsy movements; in PSP, control of motor program activation appears defective, resulting in sequence errors and perseverations. The De Renzi test can reliably estimate apraxia frequency and may be used to distinguish limb-kinetic from ideomotor apraxia.

Clinical and neuroradiological aspects of Sneddon's syndrome and primary antiphospholipid antibody syndrome. A follow-up study

Abstract We performed a study to investigate differences and similarities between patients with Sneddons syndrome and those with primary antiphospolipid syndrome (PAS), by clinical follow-up, magnetic resonance imaging (MRI) and angiography. Nine patients with Sneddons syndrome and 11 patients with PAS were assessed at diagnosis and followed for a mean fo 6 years. The clinical and MRI findings indicated that Sneddons syndrome and PAS are distinct entities. Patients with Sneddons syndrome had a progressive clinical course with increasing disability and cognitive deterioration; patients with PAS had a more benign course. Infarcts in territories of the main cerebral arteries were frequent in PAS, while leukoaraiosis and smaller lacunar infacts were more comon in Sneddons syndrome. In 3 of 7 women initially diagnosed with PAS, the diagnosis was changed to systemic lupus erythematosus during follow-up. Differential diagnosis of Sneddons syndrome and PAS is important, as early therapy is effective for the latter, more benign, condition.

Longitudinal study of cognitive and psychiatric functions in spinocerebellar ataxia types 1 and 2

The role of the cerebellum in cognition, both in healthy subjects and in patients with cerebellar diseases, is debated. Neuropsychological studies in spinocerebellar ataxia type 1 (SCA1) and type 2 (SCA2) demonstrated impairments in executive functions, verbal memory, and visuospatial performances, but prospective evaluations are not available. Our aims were to assess progression of cognitive and psychiatric functions in patients with SCA1 and SCA2 in a longitudinal study. We evaluated at baseline 20 patients with SCA1, 22 patients with SCA2 and 17 matched controls. Two subgroups of patients (9 SCA1, 11 SCA2) were re-evaluated after 2xa0years. We tested cognitive functions (Mini Mental State Examination, digit span, Corsi span, verbal memory, attentional matrices, modified Wisconsin Card Sorting Test, Raven Progressive Matrices, Benton test, phonemic and semantic fluency), psychiatric status (Scales for Assessment of Negative and Positive Symptoms, Hamilton Depression and Anxiety Scales), neurological conditions (Scale for Assessment and Rating of Ataxia), and functional abilities (Unified Huntington Disease Rating Scale–part IV). At baseline, SCA1 and SCA2 patients had significant deficits compared to controls, mainly in executive functions (phonemic and semantic fluencies, attentional matrices); SCA2 showed further impairment in visuospatial and visuoperceptive tests (Raven matrices, Benton test, Corsi span). Both SCA groups had higher depression and negative symptoms, particularly apathy, compared to controls. After 2xa0years, motor and functional disability worsened, while only attentive performances deterioratedxa0in SCA2. This longitudinal study showed dissociation in progression of motor disability and cognitive impairment, suggesting that in SCA1 and SCA2 motor and cognitive functions might be involved with different progression rates.