Francisco Cardoso

Outcome after stereotactic thalamotomy for parkinsonian, essential, and other types of tremor.

A better understanding of the mechanisms underlying movement disorders, coupled with refinements in surgical technique, has led to a resurgence of interest in the surgical treatment of patients with tremor. We retrospectively analyzed the outcomes of 60 patients (62 patient sides) with medically intractable tremor who underwent stereotactic thalamotomy. Of these 60 patients, 42 had Parkinsons disease (of whom 2 patients underwent bilateral surgery for a total of 44 patient sides), 6 had essential tremor, 6 had cerebellar tremor, and 6 had post-traumatic tremor. The patients received follow-up for as long as 13 years (mean, 53.4 mo) after their operations. At the most recent follow-up visit, 86% of the patients with Parkinsons disease, 83% of the patients with essential tremor, 67% of the patients with cerebellar tremor, and 50% of the patients with post-traumatic tremor had cessation of or moderate-to-marked improvement in their contralateral tremor, with a concomitant improvement in function. The mean daily dose of levodopa for those patients preoperatively taking levodopa (n = 35) was reduced by approximately 156 mg at a mean of 53.4 months after thalamotomy. Immediate postoperative complications were common, occurring in 58% of patients. The most common complications were contralateral weakness (34%), dysarthria (29%), and confusion (23%). These complications generally resolved rapidly during the postoperative period.

Anti–basal ganglia antibodies in acute and persistent Sydenham’s chorea

Objective To determine the sensitivity and specificity of methods to detect anti–basal ganglia antibodies (ABGA) in Sydenham’s chorea (SC). Background SC is a delayed manifestation of group A&bgr; hemolytic streptococcal infection typically associated with rheumatic fever (RHF). SC is characterized by chorea and motor and neuropsychiatric symptoms. Patients with SC produce antibodies that cross-react with streptococcal, caudate, and subthalamic nuclei antigens detected using an immunofluorescent (IF) method with inconsistent reports of positivity. Methods The authors developed ELISA and Western immunoblotting (WB) methods to detect ABGA and compared these assays to IF. They investigated samples from patients with acute SC (n = 20), persistent SC (n = 16), control samples from RHF (n = 16), and healthy pediatric volunteers (n = 11). Results ABGA ELISA had a sensitivity of 95% and specificity of 93% in acute SC. Both WB and IF had a sensitivity of 100% and specificity of 93%. In the persistent SC group, ABGA sensitivity dropped to 69% using WB and to 63% using IF. Three common basal ganglia antigens were identified by WB in both acute and persistent SC (40 kDa [n = 15], 45 kDa [n = 15], and 60 kDa [n = 13]). There was no antibody reactivity to cerebellum, cerebral cortex, or myelin antigen preparations in any group. Conclusions These results support the hypothesis that Syndenham’s chorea is an autoantibody-mediated disorder. Western immunoblotting and immunofluorescence are the best methods for detecting anti–basal ganglia antibodies, and reactivity to basal ganglia antigens of 40, 45, and 60 kDa were commonly seen in both acute and persistent cases of SC.

Parkinsonism and Parkinson's disease in the elderly: A community-based survey in Brazil (the Bambuí study)

Several community‐based surveys on the prevalence of Parkinsonism and Parkinsons disease have been conducted worldwide, with variations on their methodology and results. The objective of this study is to assess the prevalence of Parkinsonism and its causes in a cohort of individuals age 64 years or older in Bambuí, a Brazilian town. In phase I, 1,186 people older than 64 years responded to a 9‐question screening questionnaire for Parkinsonism. In phase II, all subjects who scored ≥ 2 points on the test were examined independently by at least 2 movement disorder‐trained physicians. A movement disorder senior specialist excluded or confirmed the diagnosis in all suspected cases. The response rate was high for both phases (96% for phase I and 94% for phase II). The prevalence rate per 100 population over 64 years of age in this group was 7.2% for Parkinsonism of all types (n = 86). The most frequent causes were idiopathic Parkinsons disease and drug‐induced Parkinsonism, with prevalence rates of 3.3% (n = 39) and 2.7% (n = 32), respectively. The prevalence of vascular Parkinsonism was 1.1% (n = 13). We found 1 case of posttraumatic Parkinsonism and another with multiple system atrophy. In this first population‐based study of Parkinsonism conducted in Brazil, the prevalence in a cohort of elderly subjects was higher than the observed in other populations worldwide, especially because of the high rates of drug‐induced and vascular Parkinsonism. The prevalence of Parkinsons disease was similar to that observed in elderly people in door‐to‐door surveys in other American, European, and Eastern countries.

Poststreptococcal acute disseminated encephalomyelitis with basal ganglia involvement and auto‐reactive antibasal ganglia antibodies

Antibasal ganglia antibodies (ABGA) are associated with Sydenhams chorea and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. We present 10 patients with acute disseminated encephalomyelitis (ADEM) associated with Group A β hemolytic streptococcal infection. The clinical phenotype was novel, with 50% having a dystonic extrapyramidal movement disorder, and 70% a behavioral syndrome. None of the patients had rheumatic fever or Sydenhams chorea. Enzyme‐linked immunosorbent assay, Western immunoblotting, and immunohistochemistry were used to detect ABGA. Neurological (n = 40) and streptococcal (n = 40) controls were used for comparison. Enzyme‐linked immunosorbent assay results showed significantly elevated ABGA in the patients with poststreptococcal ADEM. Western immunoblotting demonstrated ABGA reactivity to three dominant protein bands of 60, 67, or 80 kDa; a finding not reproduced in controls. Fluorescent immunohistochemistry demonstrated specific binding to large striatal neurones, which was not seen in controls. Streptococcal serology was also significantly elevated in the poststreptococcal ADEM group compared with neurological controls. Magnetic resonance imaging studies showed hyperintense basal ganglia in 80% of patients with poststreptococcal ADEM, compared to 18% of patients with nonstreptococcal ADEM. These findings support a new subgroup of postinfectious autoimmune inflammatory disorders associated with Group A β hemolytic streptococcus, abnormal basal ganglia imaging, and elevated ABGA.

Seminar on choreas

Chorea is one of the major types of involuntary movement disorders originating from dysfunctional neuronal networks interconnecting the basal ganglia and frontal cortical motor areas. The syndrome is characterised by a continuous flow of random, brief, involuntary muscle contractions and can result from a wide variety of causes. Diagnostic work-up can be straightforward in patients with a positive family history of Huntingtons disease or acute-onset hemichorea in patients with lacunar stroke, but it can be a challenging and complex task in rare autoimmune or genetic choreas. Principles of management focus on establishing an aetiological classification and, if possible, removal of the cause. Preventive strategies may be possible in Huntingtons disease where genetic counselling plays a major part. In this review we summarise the current understanding of the neuroanatomy and pathophysiology of chorea, its major aetiological classes, and principles of diagnostic work-up and management.

DYT16, a novel young-onset dystonia-parkinsonism disorder: identification of a segregating mutation in the stress-response protein PRKRA

BACKGROUND Dystonia and parkinsonism may present as part of the same genetic disorder. Identification of the genetic mutations that underlie these diseases may help to shed light on the aetiological processes involved. METHODS We identified two unrelated families with members with an apparent autosomal recessive, novel, young-onset, generalised form of dystonia parkinsonism. We did autozygosity mapping and candidate gene sequencing in these families. FINDINGS High-density genome-wide SNP genotyping revealed a disease-segregating region containing 277 homozygous markers identical by state across all affected members from both families. This novel disease locus, designated DYT16, covers 1.2 Mb at chromosome 2q31.2. The crucial interval contains 11 genes or predicted transcripts. Sequence analysis of every exon of all of these transcripts revealed a single disease-segregating mutation, c.665C>T (P222L), in the stress-response gene PRKRA, which encodes the protein kinase, interferon-inducible double-stranded RNA-dependent activator. INTERPRETATION We describe a mutation within the gene PRKRA that segregates with a novel, autosomal recessive, dystonia parkinsonism syndrome. These patients have progressive, generalised, early-onset dystonia with axial muscle involvement, oromandibular (sardonic smile), laryngeal dystonia and, in some cases, parkinsonian features, and do not respond to levodopa therapy.

Persistent Sydenham's chorea.

Sydenhams chorea (SC) occurs in 26% of patients with rheumatic fever (RF). Despite usually being described as a self‐limited condition, few reports indicate that SC may persist in rare subjects.

Impact of an Exercise Program on Physical, Emotional, and Social Aspects of Quality of Life of Individuals With Parkinson's Disease

We evaluated changes in different domains of quality of life (QL) for persons with Parkinsons disease after a program of physical activity. Twenty subjects with a diagnosis of Parkinsons disease classified as Stages 1 to 3 on the Hoehn and Yahr scale and with a mean age of 61.5 ± 9.8 years participated in 36 group sessions of a combined group program of aerobic conditioning and muscular strengthening. QL was investigated by the Nottingham Health Profile, a generic questionnaire composed of six domains. Students paired t tests indicated significant gains associated with the program (P < 0.05) on the total score and those related to emotional reactions (ER), social interactions (SI), and physical ability (PA). SI was the domain that showed the greatest program gains (41.4%). The program of physical activity performed with persons with Parkinsons disease at light to moderate stages resulted in improvements in their perception of QL, mainly in the domains of ER, SI, and PA.

Obsessive compulsive behavior, hyperactivity, and attention deficit disorder in Sydenham chorea.

The authors investigated obsessive-compulsive behavior, obsessive-compulsive disorder (OCD), and attention deficit and hyperactivity disorder (ADHD) in 50 healthy subjects, 50 patients with rheumatic fever without chorea, and 56 patients with Sydenham chorea. Obsessive-compulsive behavior, OCD, and ADHD were more frequent in the Sydenham chorea group (19%, 23.2%, 30.4%) than in the healthy subjects (11%, 4%, 8%) and in the rheumatic fever without chorea group (14%, 6%, 8%). ADHD was more common in persistent Sydenham chorea.

Increased serum levels of soluble tumor necrosis factor-α receptor-1 in patients with Parkinson's disease

Parkinsons disease (PD) is characterized by a progressive and irreversible loss of dopaminergic neurons. Inflammatory mechanisms have been implied in the pathophysiology of PD. In this study, we assessed serum levels of TNF-alpha and the soluble forms of their receptors, sTNFR1 and sTNFR2, in 46 PD patients and 23 control subjects. Patients with PD had higher levels of sTNFR1 (p=0.048). The concentration of sTNFR1 and sTNFR2 correlated with age (p=0.006 and p=0.022, respectively). Higher levels of sTNFR1 were associated with later disease onset (p=0.048). These results corroborate the role of inflammatory events in the process of neurodegeneration in PD which can be of special relevance in the sporadic form of PD with later onset.