Tyrosine hydroxylase deficiency in three Greek patients with a common ancestral mutation

We present the clinical, biochemical, and molecular findings of three Greek patients with tyrosine hydroxylase (TH) deficiency. All patients presented with a severe clinical phenotype characterized by prominent motor delay, infantile parkinsonism, oculogyric crises, and signs of autonomic dysfunction. Cerebrospinal fluid analysis disclosed reduced dopamine metabolites and normal pterins. Response to levodopa was favorable though not dramatic. All patients were homozygous for a previously reported mutation (p.L236P). SNP haplotype analysis was consistent with a common ancestral mutation, thus indicating a founder effect in Greek patients with TH deficiency. © 2010 Movement Disorder Society     

Impaired sense of smell and color discrimination in monogenic and idiopathic Parkinson's disease

Olfaction is typically impaired in idiopathic Parkinson's disease (IPD), but its role is uncertain in monogenic PD. Diminished color discrimination has been suggested as another early sign of dopaminergic dysfunction but not been systematically studied. Furthermore, it is unknown whether both deficits are linked. We examined 100 patients with IPD, 27 manifesting mutation carriers (MC), 20 nonmanifesting mutation carriers (NMC), and 110 controls. Participants underwent a standardized neurological examination, the University of Pennsylvania Smell Identification Test (UPSIT), the Farnsworth‐Munsell (FM) color discrimination test, and mutation testing in known PD genes. The monogenic group consisted of 15 Parkin (6MC/9NMC), 17 PINK1 (10MC/7NMC), 8 LRRK2 (4MC/4NMC), 3 SNCA (MC), and 4 ATP13A2 (MC) carriers. Olfaction was most impaired in IPD (UPSIT percentiles 10.1 ± 13.5) compared with all other groups (MC 13.8 ± 11.9, NMC 19.6 ± 13.0, controls 33.8 ± 22.4). Within MC, carriers of two mutations in Parkin and PINK1 showed higher UPSIT percentiles than LRRK2 and SNCA carriers. Color discrimination was reduced in IPD (FM total error score 134.8 ± 92.7). In MC (122.4 ± 142.4), the reduction was most pronounced in LRRK2, NMC (80.0 ± 38.8) were comparable with controls (97.2 ± 61.1). UPSIT and FM scores were correlated in the control (r = ?0.305; P = 0.002) and the IPD group (r = ?0.303; P = 0.006) but not among mutation carriers. First, we confirmed olfaction and color discrimination to be impaired in IPD and suggest olfaction to be a premotor sign. Second, olfaction differed between carriers with one and two mutations in Parkin/PINK1‐associated PD. Third, olfaction and color discrimination impairment do not necessarily evolve in parallel. © 2010 Movement Disorder Society     

Psychogenic parkinsonism: a combination of clinical, electrophysiological, and [(123)I]-FP-CIT SPECT scan explorations improves diagnostic accuracy.

We evaluated the concordance between independent clinical, electrophysiological, and [(123)I]-FP-CIT SPECT scan explorations as a staged procedure for an accurate diagnosis in 9 patients referred with a diagnosis of suspected psychogenic parkinsonism. Three patients were reclassified as pure psychogenic parkinsonism (PP), 6 with a form of combined psychogenic parkinsonism and Parkinson's disease (PP + PD), and none with pure Parkinson's disease (PD). Electrophysiological recordings showed the characteristics of psychogenic tremor in 5 of 7 patients with tremor. In two of these 5, PD tremor was also recorded. SPECT scan results were abnormal in five of 9 patients. In one case of clinically suspected PP + PD, SPECT scan results were normal. Long-term follow-up supported the final diagnosis of PP (initial clinical misdiagnosis). Electrophysiology contributes to the clinical diagnosis of psychogenic tremor and may help confirm associated organic PD tremor. [(123)I]-FP-CIT SPECT is a robust test to ascertain dopaminergic denervation and increase the confidence of the clinical and electrophysiological diagnosis of associated PD. A combination of clinical, electrophysiological, and [(123)I]-FP-CIT SPECT scan explorations improves diagnostic accuracy in order to distinguish PP from PP + PD.     

依达拉奉治疗血管性帕金森综合征的疗效观察

目的 评定依达拉奉治疗血管性帕金森综合征的临床疗效。方法 入选85例病人，随机分为治疗组45例、对照组40例，2组病人诊断符合血管性帕金森综合征的诊断标准，年龄、性别、症状、体征及病程等具有可比性。对照组给予美多巴片，疗程12周；治疗组给予依达拉奉注射液、美多巴片，疗程12周。12周后观察临床疗效。结果 依达拉奉组疗效明显优于美多巴组。结论 依达拉奉治疗血管性帕金森综合征效果满意，有应用价值。     

Radiotherapy to the salivary glands as treatment of sialorrhea in patients with parkinsonism.

This study investigated retrospectively the long-term efficacy and safety of radiotherapy (RT) to the major salivary glands as treatment of sialorrhea in patients with parkinsonism. Twenty-eight patients received a bilateral dose of 12 Gy to the parotid and part of the submandibular glands between 2001 and 2006. Severity of sialorrhea and adverse events were assessed at 1 and 6 months post-RT and finally in the first quarter of 2007. Item 6 of the activities of daily living-section of the Unified Parkinson's Disease Rating Scale was used as primary endpoint. Quality of life (QoL) pre- and post-RT was investigated using a shortened Parkinson's Disease Questionnaire-8. Sialorrhea had improved significantly at 1 month post-RT and this effect was maintained for at least 1 year. Most frequent adverse events were loss of taste and a dry mouth; however, 75% of these adverse events were transient. QoL had improved significantly on the long term. The clinical global impression scores at the final follow-up showed that 80% of patients were satisfied. It was concluded that RT is an effective and safe treatment of sialorrhea on the long term in patients with parkinsonism.     

Factor structure of parkinsonian signs in the community-dwelling elderly.

Parkinsonian signs are present in 40% of older people. Factor analysis of the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS) in patients with Parkinson's disease (PD) has identified several principal domains, including rigidity, axial function, and rest tremor. We hypothesized that if Parkinsonian signs in the elderly were due to basal ganglia dysfunction that this same constellation of factors (rigidity, axial function, rest tremor) would emerge in a factor analysis. We carried out factor analysis, using the principal component method with orthogonal (varimax) rotation, on motor UPDRS scores in community-dwelling elderly without PD. A modified (10-item) version of the motor portion of the UPDRS was administered to 1,339 older adults living in the Washington Heights-Inwood community and it was found that Parkinsonian signs were present in 537 (40.1%). Three factors (rigidity, axial function. and rest tremor) were obtained from the factor analysis and, together, explained 67.4% of the variance. A second factor analysis was carried out excluding the 26 participants with rest tremor, and two factors (rigidity, axial function) emerged. These data support the view that Parkinsonian signs in older adults might be due to basal ganglia dysfunction, a possibility that requires further exploration.     

The effect of quetiapine on psychosis and motor function in parkinsonian patients with and without dementia.

Recently, several small studies have indicated that quetiapine may be useful in the treatment of drug-induced psychosis in patients with PD. However, there have been questions related to atypical antipsychotic therapy and patient selection and how that may affect response and tolerability, especially worsening of the motor symptoms of PD. In particular, the presence or absence of dementia seems to be important. The aim of this study was to evaluate the effect of quetiapine on psychosis and motor symptoms in PD patients with and without dementia. A retrospective record review of patient responses to quetiapine was conducted. Response of psychosis was assessed through patient and caregiver interviews. Motor symptom change in relation to this therapy was assessed by patient and caregiver interviews and completion of the motor portion of the Unified Parkinson's Disease Rating Scale (UPDRSm). Analysis was performed by comparing psychosis and motor feature measures from before and after therapy for the group as a whole and for demented and nondemented subgroups, using nonparametric tests and Fisher's exact test. Forty-three consecutively treated PD patients were evaluated. The mean dose of quetiapine was 54 mg per day and the duration of therapy was 10 months. Eighty-one percent of patients demonstrated partial or complete amelioration of psychosis. Five patients (13%) experienced a worsening of PD motor symptoms, which was corroborated by changes seen in UPDRSm. When the group was examined as a whole, no significant change in UPDRSm score was noted. When demented (n = 20) and nondemented (n = 19) patients were compared, improvement in psychosis occurred in similar numbers of patients, but a significant difference in the numbers of patients who experienced a worsening of motor symptoms was seen (P < 0.02, Fisher's exact test). All five patients who complained of motor worsening were in the demented group. UPDRSm score after therapy tended to be worse in the demented group (P = 0.55, Mann-Whitney U test). There was no significant change in the levodopa dose. Approximately 80% of patients chose to continue therapy. We conclude that quetiapine is effective in improving psychosis in approximately 80% of PD patients both with and without dementia. Patients with dementia seem to have a higher propensity for worsening of motor symptoms.     

SCA2 and SCA3 mutations in young-onset dopa-responsive parkinsonism

In this study no one of our 85 patients of Serbian origin with young-onset (≤ 45 years) dopa-responsive parkinsonism (YOP), previously proved negative for PARK1 and PARK2 mutations, had either spinocerebellar ataxia type 2 (SCA2) or SCA3 mutation. These data do not prove the significance of these two mutations in either sporadic or familial YOP suggestive of Parkinson's disease.     

Thiethylperazine-induced parkinsonism: in vivo demonstration of dopamine D2 receptors blockade

Thiethylperazine (Torecan) is a piperazine phenothiazine employed to relieve vertigo. Its use may be associated with extrapyramidal side effects (dystonia, akathisia, tardive dyskinesia) (Sulkava, 1984), but parkinsonism has rarely been described. We describe a woman who, 1 month after the onset of thiethylperazine treatment, developed parkinsonism that disappeared 2 months after withdrawal of the drug. However, cerebral single-photon emission computed tomography (SPECT) with the dopamine (DA) D2 receptors ligand 123I-iodobenzamide (123I-IBZM) revealed a persistent reduced DA D2 receptors activity (by 45%) in the basal ganglia (BG), which may be clinically not effective.     

Dressing apraxia in corticobasal degeneration

The present paper considers a patient with corticobasal degeneration and dressing apraxia. A 65-year-old woman developed difficulties in housekeeping 3 months prior to admission. Neurological examinations revealed mild dementia and asymmetric parkinsonism; the most conspicuous feature was dressing apraxia with constructive disabilities. Magnetic resonance imaging showed right temporoparietal atrophy. A 3-D brain perfusion imaging demonstrated a decrease in cerebral blood flow in the right perirolandic and perisylvian regions. These clinical and neuroimaging findings were compatible with corticobasal degeneration. Although various types of apraxia are associated with corticobasal degeneration, dressing apraxia has rarely been reported. Our case indicates that dressing apraxia can manifest as another neuropsychiatric problem in corticobasal degeneration if coexistent movement disorders remain mild early in the stage of the illness.