Abstract: ABSTRACT: We describe a 64-year-old patient affected by multiple system atrophy (MSA) whose symptoms of cerebellar ataxia were temporarily markedly worsened by smoking a cigarette. Interestingly, a similar phenomenon was reported in the original description of MSA by Graham and Oppenheimer in 1969, although never again since then. Cholinergic involvement is present in MSA, as shown by recent pathological and functional neuroimaging studies. Further studies are warranted to investigate the prevalence of nicotine sensitivity in MSA and shed light on its neurochemical substrate.
Abstract: To evaluate the prevalence of psychosis associated with Parkinson's disease (PSY-PD) in its early stages, its incidence over a 24 month follow-up period and the association with motor and non-motor clinical features.
Abstract: We designed this study to find out more about the relationship between the sensory effects of Botulinum toxin type A (BTX) and the clinical benefits of BTX therapy in patients with cervical dystonia (CD). In 24 patients with CD, we tested sensory temporal discrimination (STD) in the affected and two unaffected body regions (neck, hand, and eye) before and 1 month after BTX injection. In 8 out of the 24 patients with CD, STDT values were tested bilaterally in the three body regions before, 1 and 2 months after BTX injection. As expected, STD testing disclosed altered STD threshold values in all three body regions tested (affected and unaffected by dystonic spasms) in patients with CD. STD threshold values remained unchanged at all time points of the follow-up in all CD patients. The lack of BTX-induced effects on STD thresholds suggests that STD recruits neural structures uninvolved in muscle spindle afferent activation.
Abstract: Multiple system atrophy (MSA) is a neurodegenerative disease characterized clinically by a combination of parkinsonian, cerebellar, autonomic and pyramidal features. Recent data show that the MSA clinical spectrum is wider than was originally thought, and may include various nonmotor symptoms that arise at disease onset. These symptoms include urinary disorders, erectile dysfunction in men, orthostatic hypotension, sleep disruption, stridor, and severe constipation. Neurologists and other specialists must be made aware that this relatively common neurodegenerative disease can manifest with nonmotor symptoms well before patients develop any overt motor disorder. The importance of recognizing such symptoms should not be underestimated, being crucial for understanding the disease prognosis, avoiding unnecessary tests and procedures, and planning any therapeutic intervention.
Abstract: Findings of standard MR imaging examinations are usually normal in primary CD. These findings are now increasingly challenged by studies using advanced neuroimaging techniques detecting abnormalities in brain areas that may be functionally involved in the pathophysiology of CD. Our purpose was to evaluate GM volumes in patients with CD at baseline and 5 years later.
Abstract: Dystonia is defined as a motor syndrome characterized by sustained muscle contractions, usually producing twisting and repetitive movements or abnormal postures. Dystonia can be present at rest or worsened by action. Dystonia is commonly classified according to age at onset (childhood, adolescent type, and adult type), etiology (idiopathic, and symptomatic), and distribution (focal dystonia, segmental dystonia, generalized dystonia, multifocal dystonia and hemidystonia). The different subtypes of focal and segmental dystonias may have different clinical features. Neuropsychiatric disorders may be present in dystonia.
Abstract: No study has yet investigated whether cortical plasticity in primary motor area (M1) is abnormal in patients with progressive supranuclear palsy (PSP). We studied M1 plasticity in 15 PSP patients and 15 age-matched healthy subjects. We used intermittent theta-burst stimulation (iTBS) to investigate long-term potentiation (LTP) and continuous TBS (cTBS) to investigate long-term depression (LTD)-like cortical plasticity in M1. Ten patients underwent iTBS again 1 year later. We also investigated short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) in M1 with paired-pulse transcranial magnetic stimulation, tested H reflex from upper limb flexor muscles before and after iTBS, and measured motor evoked potential (MEP) input-output (I/O) curves before and after iTBS. iTBS elicited a significantly larger MEP facilitation after iTBS in patients than in healthy subjects. Whereas in healthy subjects, cTBS inhibited MEP, in patients it significantly facilitated MEPs. In patients, SICI was reduced, whereas ICF was normal. H reflex size remained unchanged after iTBS. Patients had steeper MEP I/O slopes than healthy subjects at baseline and became even more steeper after iTBS only in patients. The iTBS-induced abnormal MEP facilitation in PSP persisted at 1-year follow-up. In conclusion, patients with PSP have abnormal M1 LTP/LTD-like plasticity. The enhanced LTP-like cortical synaptic plasticity parallels disease progression.
Abstract: Using data from the PRIAMO study, we investigated non-motor symptoms (NMS) versus frontal lobe dysfunction in patients with idiopathic Parkinson disease (PD); 808 patients with PD and 118 with atypical parkinsonisms (AP) were consecutively enrolled at 55 Centers in Italy. Twelve categories of NMS were investigated. Cognitive impairment was defined as a Mini-Mental Status Evaluation score ≤23.8 and frontal lobe dysfunction as a Frontal Assessment Battery (FAB) score ≤13.48. Multivariable logistic regression was used to identify predictor of frontal lobe dysfunction in 524 PD patients, and a generalized linear model was used for each of the six FAB items. Not only the total FAB scores but also the single FAB items were lower in AP versus PD (p ≤ 0.005). Age (OR = 1.05), cognitive impairment (OR = 9.54), lack of cardiovascular symptoms (OR = 3.25), attention or memory problems (OR = 0.59) and treatment with L: -DOPA (OR = 5.58) were predictors of frontal lobe dysfunction. MMSE was negatively associated with all FAB items (β ≤ -0.16) and age with all FAB items but prehension behavior (β ≤ -0.01). Previous use of L: -DOPA was negatively associated with verbal fluency (β = -0.32) possibly acting as surrogate marker of disease duration. Cognitive impairment is a predictor of frontal lobe dysfunction. Among NMS, lack of attention or memory problems were negatively associated with frontal impairment. Further studies are nonetheless needed to better identify the predictors of frontal impairment in PD patients.
Abstract: In Parkinson's disease (PD) the urinary dysfunction manifests primarily with symptoms of overactive bladder (OAB). The OAB questionnaire (OAB-q) is a measure designed to assess the impact of OAB symptoms on health-related quality of life. In this study, we quantified the urinary symptoms in a large cohort of PD patients by using the OAB-q short form. Possible correlations between the OAB-q and clinical features were tested. Three hundred and two PD patients were enrolled in the study. Correlations between the OAB-q and sex, age, Unified Parkinson's Disease Rating Scale part III (UPDRS-III), Hoehn-Yahr (H-Y) staging, disease duration, and treatment were analyzed. Data were compared with a large cohort of 303 age-matched healthy subjects. The OAB-q yielded significantly higher scores in PD patients than in healthy subjects. In the group of PD patients, all the variables tested were similar between men and women. Pearson's coefficient showed a significant correlation between mean age, disease duration, mean OAB-q scores, UPDRS-III scores, and H-Y staging. A multiple linear regression analysis showed that OAB-q values were significantly influenced by age and UPDRS-III. No statistical correlations were found between OAB-q scores and drug therapy or the equivalent levodopa dose, whilst the items relating to the nocturia symptoms were significantly associated with the equivalent levodopa dose. Our findings suggest that bladder dysfunction assessed by OAB-q mainly correlates with UPDRS-III scores for severity of motor impairment, possibly reflecting the known role of the decline in nigrostriatal dopaminergic function in bladder dysfunction associated with PD and patients' age. Our study also suggests that the OAB-q is a simple, easily administered test that can objectively evaluate bladder function in patients with PD.
Abstract: In a single-center, case-control study, we investigated the frequency and types of psychiatric disturbances in 89 consecutive patients with various primary focal dystonias (34 had cervical dystonia (CD), 28 blepharospasm (BPS), 16 laryngeal dystonia (LD), and 11 arm dystonia), 62 healthy control subjects and as controls for BPS, 26 patients with hemifacial spasm (HFS). Patients and controls underwent a full psychiatric evaluation. Diagnosis was based on the structured clinical interview for DSM-IV, obsessive-compulsive disorder (OCD) was assessed with the Yale-Brown Obsessive-Compulsive scale, anxiety with the Hamilton Rating Scale for Anxiety, the severity of depression with the Beck Depression Inventory. Of the 89 patients with focal dystonias studied, 51 patients (57.3%) had a diagnosis of psychiatric disorders compared with only 15 of 62 healthy subjects (24.1%) and 9 of the patients with HFS (34.6%). Depressive disorders were more frequent in the CD and BPS groups than in healthy controls, whereas the frequency of anxiety disorders, OCDs or adjustment disorders approached that of healthy subjects. No difference was found in the frequency of any specific psychiatric disorder in patients with LD and arm dystonia and healthy controls. In 35 of 51 patients who had psychiatric disorders, these started before and in 16 patients after the onset of dystonia. No differences were found in age, dystonia severity, and duration of botulinum toxin treatment between patients with and without psychiatric disturbances. The most common psychiatric features in patients with CD and BPS are depressive disorders.
Abstract: Drug-induced dyskinesia is a common phenomenon in Parkinson's disease (PD) and is often socially as well as physically disabling for patients. The Movement Disorders Society commissioned a task force to assess available clinical rating scales, critique their clinimetric properties, and make recommendations regarding their clinical utility. A task force composed six clinical researchers who systematically searched the literature for scales measuring dyskinesia in PD, evaluated the scales' previous use, performance parameters, and quality of validation data (if available). A scale was designated "Recommended" if the scale has been used in clinical studies beyond the group that developed it, has been specifically used in PD reports, and if clinimetric studies have established that it is a valid, reliable, and sensitive. "Suggested" scales met two of the above criteria and those meeting one were "Listed." Based on the systematic review, eight rating scales for dyskinesia that have either been validated or used in PD were identified. These were the Abnormal Involuntary Movement Scale (AIMS), The Unified Parkinson's Disease Rating Scale (UPDRS) part IV, the Obeso Dyskinesia Rating Scale, the Rush Dyskinesia Rating Scale, the Clinical Dyskinesia Rating Scale (CDRS), the Lang-Fahn Activities of Daily Living Dyskinesia Scale, the Parkinson Disease Dyskinesia Scale (PDYS-26), and the Unified Dyskinesia Rating Scale (UDysRS). Based on this review, at present two of the reviewed dyskinesia scales (AIMS and the Rush Dyskinesia Rating Scale) fulfill criteria for Recommended for use in PD populations, albeit weakly so; all of the remaining met criteria to be Suggested. However, the two most recent scales (PDYS-26 and UDysRS) have excellent clinimetric properties and appear to provide a reliable and valid assessment tool of dyskinesia in PD. If they are used successfully beyond the groups that developed them, both have the potential to be re-ranked as Recommended. As further testing of these scales in PD is warranted, no new scales are needed until the available scales are fully tested clinimetrically.
Abstract: Essential tremor (ET) and migraine headache are considered comorbid diseases on the basis of uncontrolled studies. We investigated the frequency of migraine in patients with ET by enrolling 110 patients with ET and 110 age- and sex-matched healthy controls in a case-control study. We found no significant differences in the frequency of lifetime and current migraine between patients and controls, even in patients stratified for age. Tremor had similar clinical features in patients with ET with and without migraine except that females predominated in patients with ET and migraine. Migraine also had similar characteristics in both patients with ET and migraine and in controls with migraine. Our study excludes a comorbid association between ET and migraine. When ET and migraine coexist their clinical phenotype and evolution remain almost unchanged.
Abstract: 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.
Abstract: Blepharospasm, oromandibular, lingual, laryngeal and cervical dystonia are common forms of adult-onset dystonia. Each condition may appear in isolation or manifest along with other forms of craniocervical dystonia. Although the various craniocervical dystonias typically present with involuntary muscle spasms causing abnormal postures, they differ for some clinical features. Neurophysiologic and neuroimaging studies have shown a number of motor and sensory abnormalities at cortical and subcortical levels, probably reflecting a dysfunction in the basal ganglia-thalamo-cortical circuits. The best treatment for craniocervical dystonia is botulinum toxin injected into the overactive muscles.
Abstract: Edouard Brissaud (1852-1909) was a French neuropsychiatrist of the Charcot school who provided in 1893 the first picture of a patient suffering from hemifacial spasm. Brissaud already suggested several possible etiologies for the involuntary movements of his patient, including the possibility of arterial malformations compressing the origin of the facial nerve. We also discuss the role of other early European authors (Schültze, Gowers, Babinski, and Negro) who contributed to the definition of hemifacial spasm in the late 19th and early 20th centuries.
Abstract: The atypical parkinsonian disorders (APD) embrace a heterogeneous group of movement disorders all characterized by prominent parkinsonism, accompanied by specific additional features such as cerebellar ataxia, early autonomic dysfunction, early dementia, pyramidal tract signs, myoclonus, supranuclear gaze palsy, apraxia which are atypical for idiopathic Parkinson's disease (PD). Beside these features, rapid disease progression and poor or absent response to L-Dopa therapy both raise the suspicion of an APD. Currently, multiple system atrophy (MSA), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and dementia with Lewy bodies (DLB) are referred to as APD. Clinical diagnosis can be difficult in early stages and although the predictive value of the widely established, diagnostic criteria is high at first neurological evaluation sensitivity tends to be poor and may be less than 30%. In this review, we will discuss diagnostic issues in MSA and PSP.
Abstract: Multiple system atrophy (MSA) is a Parkinson's Disease (PD)-like α-synucleinopathy clinically characterized by dysautonomia, parkinsonism, cerebellar ataxia, and pyramidal signs in any combination. We aimed to determine whether the clinical presentation of MSA as well as diagnostic and therapeutic strategies differ across Europe and Israel. In 19 European MSA Study Group centres all consecutive patients with a clinical diagnosis of MSA were recruited from 2001 to 2005. A standardized minimal data set was obtained from all patients. Four-hundred thirty-seven MSA patients from 19 centres in 10 countries were included. Mean age at onset was 57.8 years; mean disease duration at inclusion was 5.8 years. According to the consensus criteria 68% were classified as parkinsonian type (MSA-P) and 32% as cerebellar type (MSA-C) (probable MSA: 72%, possible MSA: 28%). Symptomatic dysautonomia was present in almost all patients, and urinary dysfunction (83%) more common than symptomatic orthostatic hypotension (75%). Cerebellar ataxia was present in 64%, and parkinsonism in 87%, of all cases. No significant differences in the clinical presentation were observed between the participating countries. In contrast, diagnostic work up and therapeutic strategies were heterogeneous. Less than a third of patients with documented orthostatic hypotension or neurogenic bladder disturbance were receiving treatment. This largest clinical series of MSA patients reported so far shows that the disease presents uniformly across Europe. The observed differences in diagnostic and therapeutic management including lack of therapy for dysautonomia emphasize the need for future guidelines in these areas.
Abstract: We retrospectively investigated in consecutive Parkinson's disease (PD) outpatients the relationship between the body region in which LID first appeared and the body region where Parkinsonian motor symptoms started. We also studied the spread of LID and motor symptoms to other body parts during the progression of PD. Of the 307 PD patients investigated, 99 with LID were enrolled in the study. In these 99 patients, LID started unilaterally in the limbs in 44, bilaterally in the limbs in 26, and in craniocervical region in 29, whereas motor symptoms invariably started in the limbs. LID and motor symptoms started in the same body region in less than half of the patients studied. Of the 99 patients studied, 69 had LID spread to at least another body region during the course of their disease. In this group, clinical examination yielded a significantly different distribution of LID and motor symptoms. These findings suggest that the onset and spread of LID and motor symptoms may follow different anatomical patterns.
Abstract: Patients with progressive supranuclear palsy (PSP) often have blinking abnormalities. In this study we examined the kinematic features of voluntary, spontaneous and reflex blinking in 11 patients with PSP and healthy control subjects. Patients were asked to blink voluntarily as fast as possible; spontaneous blinking was recorded during two 60 s rest periods; reflex blinking was evoked by electrical stimulation of the supraorbital nerve. Eyelid movements were recorded with the SMART analyzer motion system. During voluntary blinking the closing and opening phases lasted longer in patients than in healthy subjects. Furthermore, the peak velocity of the closing phase of voluntary blinking was lower in patients than healthy subjects. During spontaneous blinking the blink rate was markedly lower in patients than in control subjects. Patient's recordings also showed kinematic abnormalities of spontaneous (reduced peak velocity of both closing and opening phases) and reflex (reduced peak velocity and increased duration of the opening phase) blinking. Recordings during reflex blinking disclosed an enhanced excitability of the interneuronal pool mediating the closing and opening blink phases. Finally, the pause, a neurophysiological marker of the switching processes between the closing and opening phases, was prolonged in all the three types of blinking. The abnormal kinematic variables correlated with patients' clinical and kinematic features. Abnormal voluntary, spontaneous and reflex blinking in patients with PSP reflects the widespread cortical, subcortical and brainstem degeneration related to this disease.
Abstract: 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.
Abstract: Cranial movement disorders are a common neurological problem. These disorders can be limited to the cranial muscles alone or manifest as part of a more generalized movement disorder. Cranial movement disorders can originate from the highest (motor cortex) to the lowest (cranial nerve and muscle) levels of the motor system. Owing to the lack of diagnostic tests and biomarkers for these disorders, their differential diagnosis can be difficult even for the experienced neurologist. Advances have, however, been made in the identification and treatment of these conditions, and most can be managed effectively with appropriate knowledge of the diagnostic signs and effective treatments. Here, we review the clinical features, pathophysiologies and therapies of the main movement disorders that affect the face, jaw, tongue and palate.
Abstract: Mirror movements (MM) refer to ipsilateral involuntary movements that appear during voluntary activity in contralateral homologous body regions. This study aimed to compare the frequency and distribution of MM in an unselected sample of 274 patients with Parkinson's disease (PD) and 100 healthy subjects, and to check a possible relationship between MM and parkinsonian features. MM of the hand were scored according to the Woods and Teuber scale. The frequency of MM was lower in PD patients than in healthy subjects (29% vs. 71%, P < 0.0001). The distribution of MM also differed in the two groups being often bilateral in healthy subjects, invariably unilateral in PD patients. When parkinsonian signs were unilateral, MM always manifested on the unaffected side; when parkinsonian signs were bilateral, MM manifested on the less affected side. PD patients manifesting MM scored significantly lower on Hohen and Yahr staging than patients without MM. Likewise, there was a significant inverse correlation between the intensity of MM as rated by the Woods and Teuber score and HY staging (r = -0.16, P < 0.01). The low frequency of MM in PD probably relates to the complex interactions between the pathophysiological mechanisms leading to parkinsonian signs and the mechanisms responsible for movement lateralization.
Abstract: Primary late-onset focal dystonias may spread over time to adjacent body regions, but differences in the risk of spread over time among the various focal forms and the influence of age at dystonia onset on the risk of spread are not well established.
Abstract: The clinical diagnosis of multiple system atrophy (MSA) is fraught with difficulty and there are no pathognomonic features to discriminate the parkinsonian variant (MSA-P) from Parkinson's disease (PD). Besides the poor response to levodopa, and the additional presence of pyramidal or cerebellar signs (ataxia) or autonomic failure as major diagnostic criteria, certain other clinical features known as "red flags" or warning signs may raise the clinical suspicion of MSA. To study the diagnostic role of these features in MSA-P versus PD patients, a standardized red flag check list (RFCL) developed by the European MSA Study Group (EMSA-SG) was administered to 57 patients with probable MSA-P and 116 patients with probable PD diagnosed according to established criteria. Those red flags with a specifity over 95% were selected for further analysis. Factor analysis was applied to reduce the number of red flags. The resulting set was then applied to 17 patients with possible MSA-P who on follow-up fulfilled criteria of probable MSA-P. Red flags were grouped into related categories. With two or more of six red flag categories present specificity was 98.3% and sensitivity was 84.2% in our cohort. When applying these criteria to patients with possible MSA-P, 76.5% of them would have been correctly diagnosed as probable MSA-P 15.9 (+/-7.0) months earlier than with the Consensus criteria alone. We propose a combination of two out of six red flag categories as additional diagnostic criteria for probable MSA-P.
Abstract: Diffusion tensor imaging (DTI) analyses the movement of water molecules within the cerebral white matter thus providing information on ultrastructural brain changes. We studied 18 patients with cervical dystonia (CD), 16 with blepharospasm (BSP) and 35 years age-matched healthy controls. DTI data were obtained with a Philips 1.5 Tesla scanner and then processed to obtain maps of fractional anisotropy (FA) and mean diffusivity (MD). Twenty-three square regions of interest of uniform size were positioned on the FA maps and then automatically transferred to the MD maps. FA and MD values in the corpus callosum, left and right putamen, right caudate, left and right pre-frontal cortical area and left supplementary motor area in CD patients differed significantly from those in healthy controls. No significant regional differences were found between patients with BSP and healthy controls. In the CD group, age, duration and severity of dystonia did not correlate with regional FA/MD values, whereas the duration of botulinum toxin treatment correlated significantly with the MD value in the right-pre-frontal cortex. The abnormal DTI findings in patients with CD suggest the presence of brain ultrastructural changes in adult-onset primary CD.
Abstract: To investigate possible changes in autonomic cardiovascular regulation and cardiopulmonary baroreflex sensitivity in patients with primary cervical dystonia receiving chronic treatment with botulinum toxin type A.
Abstract: PRIAMO (PaRkinson And non Motor symptOms) is an epidemiology study aimed to assess the prevalence and incidence of non-motor symptoms (NMS) in patients with parkinsonism. PRIAMO consists of two phases: (1) a transversal assessment of the prevalence of NMS and (2) a longitudinal observation with two follow-up visits at 12 and 24 months to establish the incidence of NMS. A secondary aim of PRIAMO is to study the relationship between NMS and quality of life. Patients with parkinsonism have been evaluated in 59 Neurology Centres widely distributed throughout Italy. PRIAMO has analysed a total of 1307 patients (out of 1325 initially enrolled). We expect that PRIAMO will substantially help to quantify the burden of NMS in patients with parkinsonism.
Abstract: A consensus conference on multiple system atrophy (MSA) in 1998 established criteria for diagnosis that have been accepted widely. Since then, clinical, laboratory, neuropathologic, and imaging studies have advanced the field, requiring a fresh evaluation of diagnostic criteria. We held a second consensus conference in 2007 and present the results here.
Abstract: The relationship between prior trauma and primary adult-onset dystonia is not well understood. Previous uncontrolled observations and exploratory case-control studies have yielded contradictory results.
Abstract: Peripheral blood lymphocytes (PBL) provide a model to study the changes of neurotransmitter-receptor systems in neurodegenerative disorders, including Parkinson's disease (PD). In this study, densitometric analysis was applied to measure dopamine transporter (DAT) immunoreactivity in PBL from dopaminergic drug-free patients suffering PD or essential tremor (ET) with respect to healthy subjects. The results showed a significant reduction of DAT immunoreactivity in PBL in PD but not in ET. These finding suggests that DAT immunoreactivity in PBL may discriminate between PD and ET in the early clinical stages.
Abstract: Prior coffee and smoking habits were investigated in a multicentre case control study involving 166 patients presenting with primary late onset blepharospasm (BSP), 228 hospital control patients with primary hemifacial spasm and 187 population control subjects from five Italian centres. Information on age at disease onset, smoking and coffee drinking status at the reference age and average number of cups of coffee drunk/cigarettes smoked per day reached high and similar test-retest reproducibility in case and control patients. Unadjusted logistic regression analysis yielded a significant inverse association of prior coffee drinking and cigarette smoking with case status for the control groups. After adjustment for age, sex, referral centre, disease duration, years of schooling and ever coffee drinking/cigarette smoking, as appropriate, the smoking estimate lacked significance whereas the association of coffee intake and BSP did not (cases vs hospital control patients: OR 0.37 (95% CI 0.20 to 0.67); cases vs population control subjects: OR 0.44 (95% CI 0.23 to 0.85)). The strength of the inverse association between BSP and coffee intake tended to increase with the average number of cups drunk per day. There was a significant correlation between age of BSP onset and number of cups per day (adjusted regression coefficient 1.73; p = 0.001) whereas no correlation was found with number of packs of cigarettes per day. Coffee drinking may be inversely associated with the development of primary BSP and this association may partly depend on the amount consumed.
Abstract: For many years, levodopa has given most patients with Parkinson's disease excellent symptomatic benefit. This agent does not slow down the progression of the disease, however, and it can induce motor fluctuations and dyskinesias in the long term. The other available antiparkinsonian agents also have drawbacks, and as a consequence research into antiparkinsonian drugs is expected to take new and different directions in the coming years. The most promising approaches include the development of 'neuroprotective' drugs that are capable of blocking or at least slowing down the degenerative process that is responsible for cellular death; 'restorative' strategies intended to restore normal brain function; more-effective agents for replacing dopamine loss; and symptomatic and antidyskinetic drugs that act on neurotransmitters other than dopamine or target brain areas other than the striatum. In this Review, we discuss the numerous drugs in development that target the primary motor disorder in Parkinson's disease.
Abstract: Botulinum toxin type-A (BoNT-A) prevents the release of acetylcholine at cholinergic junctions, thereby causing temporary muscle weakness lasting 3-4 months. It is now widely used to treat a broad range of clinical disorders characterized by muscle hyperactivity. BoNT-A has proved effective in the management of several neurological conditions and, in particular, in the management of movement disorders (e.g. blepharospasm, cervical dystonia, laryngeal dystonia, limb dystonia, hemifacial spasm, focal tics, tremor and other hyperkinetic disorders). As a treatment of spasticity, BoNT-A can improve mobility and dexterity as well as preventing the development of distressing and costly secondary complications. In cerebral palsy, BoNT-A is of value, being able to delay or even avoid surgery until motion patterns have become established.
Abstract: Movement disorders of various types may occur in relation to viral infections of the central nervous system. They manifest themselves as obvious signs at clinical onset or during the acute phase of an encephalitis (myoclonus, tremor, or parkinsonism), or appear as later sequelae decades after the illness. We describe here a man who developed an unusual movement disorder after a probable viral encephalitis in his childhood. This consisted of a tremor (3-4Hz frequency and 100-150ms duration) of the neck, left shoulder and arm, which persisted unchanged during the ensuing years. The patient regarded this abnormal movement as annoying, but otherwise it did not impair his lifestyle. He subsequently developed the clinical picture of parkinsonism many decades after the onset of tremor, and we speculate that both tremor and parkinsonism can be considered sequelae of encephalitis, but each with a different time-course. The left-sided jerky tremor was an immediate sequela in the childhood; whereas, the rigid-akinetic parkinsonian picture represented a later sequela of the infection in old age. The injured site responsible for both the segmental tremor and the parkinsonism presumably involved the brainstem.
