Akinetic-rigid Research Articles

Translation Initiator EIF4G1 Mutations in Familial Parkinson Disease

Genome-wide analysis of a multi-incident family with autosomal-dominant parkinsonism has implicated a locus on chromosomal region 3q26-q28. Linkage and disease segregation is explained by a missense mutation c.3614G>A (p.Arg1205His) in eukaryotic translation initiation factor 4-gamma (EIF4G1). Subsequent sequence and genotype analysis identified EIF4G1 c.1505C>T (p.Ala502Val), c.2056G>T (p.Gly686Cys), c.3490A>C (p.Ser1164Arg), c.3589C>T (p.Arg1197Trp) and c.3614G>A (p.Arg1205His) substitutions in affected subjects with familial parkinsonism and idiopathic Lewy body disease but not in control subjects. Despite different countries of origin, persons with EIF4G1 c.1505C>T (p.Ala502Val) or c.3614G>A (p.Arg1205His) mutations appear to share haplotypes consistent with ancestral founders. eIF4G1 p.Ala502Val and p.Arg1205His disrupt eIF4E or eIF3e binding, although the wild-type protein does not, and render mutant cells more vulnerable to reactive oxidative species. EIF4G1 mutations implicate mRNA translation initiation in familial parkinsonism and highlight a convergent pathway for monogenic, toxin and perhaps virally-induced Parkinson disease.

Mitochondrial Transfer RNAPhe Mutation Associated With a Progressive Neurodegenerative Disorder Characterized by Psychiatric Disturbance, Dementia, and Akinesia-Rigidity

Mitochondrial diseases are characterized by wide phenotypic and genetic variability, but presentations in adults with akinetic rigidity and hyperkinetic movement disorders are rare. To describe clinically a subject with progressive neurodegeneration characterized by psychosis, dementia, and akinesia-rigidity, and to associate this phenotype with a novel mitochondrial transfer RNA(Phe) (tRNA(Phe)) (MTTF) mutation. Case description and detailed laboratory investigations of a 57-year-old woman at a university teaching hospital and a specialist mitochondrial diagnostic laboratory. Histopathological findings indicated that an underlying mitochondrial abnormality was responsible for the subject's progressive neurological disorder, with mitochondrial genome sequencing revealing a novel m.586G>A MTTF mutation. The clinical phenotypes associated with mitochondrial disorders may include akinesia-rigidity and psychosis. Our findings further broaden the spectrum of neurological disease associated with mitochondrial tRNA(Phe) mutations.

Voluptuary habits and clinical subtypes of Parkinson's disease: The FRAGAMP case–control study

We evaluated the possible association between smoking, coffee drinking, and alcohol consumption and Parkinson's disease (PD). The FRAGAMP study is a large Italian multicenter case-control study carried out to evaluate the possible role of environmental and genetic factors in PD. Adjusted ORs were estimated using unconditional logistic regression. Smoking, coffee, and alcohol consumption were also considered as surrogate markers of lifestyle and analysis was carried out considering the presence of at least one, two, or three factors. This latter analysis was separately performed considering Tremor-Dominant (TD) and Akinetic-Rigid (AR) patients. Four hundred ninety-two PD patients (292 men and 200 women) and 459 controls (160 men and 299 women) were enrolled in the study. Multivariate analysis showed a significant negative association between PD and cigarette smoking (OR 0.51; 95%CI 0.36-0.72), coffee drinking (OR 0.61; 95%CI 0.43-0.87) and wine consumption (OR 0.62; 95%CI 0.44-0.86); a significant trend dose-effect (P < 0.05) has been found for all the factors studied. We have also found a trend dose-effect for the presence of at least one, two or three factors with a greater risk reduction (83%) for the presence of three factors. However, a different strength of association between TD and AR was found with a greater risk reduction for the AR patients. We found a significant inverse association between PD smoking, coffee, and alcohol consumption. When analysis was carried out considering the association of these factors as possible surrogate markers of a peculiar lifestyle the association was stronger for the AR phenotype.

Course in Parkinson disease subtypes

Individual variations in the course of Lewy body Parkinson disease (PD) are well known. Patients have been classified into different clinical subtypes to identify differences in the course among the subgroups. Several studies indicate that the outcome is more favorable in tremor dominant (TD) cases but others report no difference. A majority of progression studies are based on cross-sectional single point data or short-term clinical observations. The lack of longitudinally followed autopsy-confirmed PD cohort remains a major weakness in the literature. Biochemical studies of brain indicate most pronounced abnormalities in akinetic/rigid (AR) and the least in TD cases. We postulate that PD course in these subtypes is concordant with the biochemical findings. To compare the course in TD, mixed (MX), and AR subtypes of PD. Longitudinal clinical follow-up and autopsy studies were performed on 166 patients with PD over 39 years (1968-2006). Patients were classified into TD, AR, and MX based on the entire clinical course. Only the pathologically confirmed PD cases were included. Sixty-six percent of cases had MX, 26% AR, and 8% TD profile. The age at onset was younger (p < 0.001) and progression to Hoehn & Yahr stage 4 was slower (p = 0.016) in the TD cases. Dementia was most common in AR (p = 0.039) and the least common in TD. In general, the course was most favorable in TD, followed by MX and AR subgroups. The three subtypes of Parkinson disease have different courses which are concordant with the differences in brain biochemical abnormalities.

Transcranial brain sonography findings in clinical subgroups of idiopathic Parkinson's disease

To investigate whether transcranial brain sonography (TCS) discriminates different courses of idiopathic Parkinson's disease (PD), 101 patients with clinically definite PD were studied. In four patients, TCS was not possible due to insufficient acoustic temporal bone windows. Substantia nigra (SN) hyperechogenicity was found in 96% of assessable patients. Larger SN echogenic size correlated with younger age at PD onset (Spearman correlation, r = -0.383; P < 0.001), but not with age, PD duration, or severity. Marked bilateral SN hyperechogenicity indicated early-onset rather than late-onset PD, and akinetic-rigid (AR) or mixed-type (MX) PD rather than tremor-dominant PD. SN echogenic sizes were larger contralateral to the clinically more affected side in AR PD and MX PD patients. Reduced echogenicity of brainstem raphe was associated with depression (RR = 1.61; 95% CI = 1.05-2.46; P = 0.044) but not with other clinical features. Caudate nucleus hyperechogenicity was, independently from PD duration, related to drug-induced psychosis (RR = 2.40; CI = 1.36-4.22; P = 0.001), but not to motor fluctuations. Lenticular nucleus hyperechogenicity indicated AR PD rather than tremor-dominant PD (RR = 1.44; CI = 1.11-1.86; P = 0.040). Frontal horn dilatation > 15.4 mm (mean of bilateral measurements) indicated increased risk of dementia (RR = 4.11; CI = 1.51-11.2; P = 0.001). We conclude that TCS displays characteristic changes of deep brain structures in different clinical manifestations of PD.

A Study Of MR Imaging Of The Basal Ganglia And Serum Manganese Concentration In Cirrhotic Patients With Portosystemic Shunting

Manganese in normally removed by hepatobiliary route. In long term hepatic dysfunction with portosystemic shunting it accumulates in systemic circulation and may deposit in CNS particularly in the basal ganglia, resulting in permanent extrapyramidal manifestations and a unique form of parkinsonism characterized by early gait impairment, postural fine tremor, symmetric akinetic rigidity and sometimes associated with focal dystonia (Purkhard et al., 2003). In this study: 50 male cirrhotic patients, aged 28 –59 years, were selected from Internal Medicine department – Al Hussein university hospital, in addition to 20 age-matched healthy males as a control group. All subjects (patients & controls) were submitted to (1) Full clinical & laboratory examination including liver function tests and serum manganese estimation using atomic absorption technique. (2) Abdominal triphasic spiral CT scanning for evaluation of portosystemic collaterals and to assess the hepatic intensity and the splenic size (3) MR Imaging of the brain. We have concluded that: (i) The studied cirrhotic patients had a statistically higher serum manganese concentration than that of the controls. (ii) 24/50 patients (48%) showed variable degrees of basal ganglia hyperintensity on T1- weighted MR images, associated with marked elevation of serum manganese levels (five to seven fold the normal level) and advanced grades of gastroesophageal varices on triphasic spiral CT scanning (iii) 26/50 patients (52%) showed normal intensity in the basal ganglia on T1- weighted MR images with relatively Lower levels of serum manganese (two to four fold the normal level) and early grade of gastroesophageal varices on triphasic spiral CT scanning (iv) serum manganese concentration of cirrhotic patients with hyperintensity in the basal ganglia on T1 weighted MR imaging was statistically higher than that of cirrhotic patients with normal intensity – basal ganglia.

A Study Of MR Imaging Of The Basal Ganglia And Serum Manganese Concentration In Cirrhotic Patients With Portosystemic Shunting

Manganese in normally removed by hepatobiliary route. In long term hepatic dysfunction with portosystemic shunting it accumulates in systemic circulation and may deposit in CNS particularly in the basal ganglia, resulting in permanent extrapyramidal manifestations and a unique form of parkinsonism characterized by early gait impairment, postural fine tremor, symmetric akinetic rigidity and sometimes associated with focal dystonia (Purkhard et al., 2003). In this study: 50 male cirrhotic patients, aged 28 –59 years, were selected from Internal Medicine department – Al Hussein university hospital, in addition to 20 age-matched healthy males as a control group. All subjects (patients & controls) were submitted to (1) Full clinical & laboratory examination including liver function tests and serum manganese estimation using atomic absorption technique. (2) Abdominal triphasic spiral CT scanning for evaluation of portosystemic collaterals and to assess the hepatic intensity and the splenic size (3) MR Imaging of the brain. We have concluded that: (i) The studied cirrhotic patients had a statistically higher serum manganese concentration than that of the controls. (ii) 24/50 patients (48%) showed variable degrees of basal ganglia hyperintensity on T1- weighted MR images, associated with marked elevation of serum manganese levels (five to seven fold the normal level) and advanced grades of gastroesophageal varices on triphasic spiral CT scanning (iii) 26/50 patients (52%) showed normal intensity in the basal ganglia on T1- weighted MR images with relatively Lower levels of serum manganese (two to four fold the normal level) and early grade of gastroesophageal varices on triphasic spiral CT scanning (iv) serum manganese concentration of cirrhotic patients with hyperintensity in the basal ganglia on T1 weighted MR imaging was statistically higher than that of cirrhotic patients with normal intensity – basal ganglia.

Hand rhythmic tapping and timing in Parkinson's disease

Background. Dysrhythmia is one of the features frequently associated with the motor disturbance in Parkinson's disease (PD). The mechanism responsible for this phenomenon is not known. Objectives. To assess the rhythmic movements of the hand in PD patients in general and in parkinsonian subtypes. Methods. Fifty-one PD patients (32 males) with mean age 66.3±9.1 years (6.6 years of symptoms) and 36 healthy controls (age 64.9±13.2, range 40–85) were studied. Subjects were asked to tap with their dominant or less affected arm on a digitized switch board at their most comfortable pace (16 s), fastest tapping speed (12 s), and at different frequencies provided by a metronome. The mean rhythm and the tap-to-tap variation were compared. Performance of the PD patients and control subjects were compared, as there were different subtypes of PD patients. Patients were subclassified into: tremor predominant (TP) (14 patients), freezing predominant (FP) (11 patients), akinetic-rigid (AR) (12 patients) and an unclassified group (UC) (14 patients). Results. There was no significance difference between patients and controls in the self-chosen, most comfortable tapping rate or in the tap-to-tap variation of the self-paced task. PD patients tapped at a significantly slower rate than controls when asked to tap at their fastest rate (4.39±1.32 vs. 5.14±1.31 Hz; p<0.01). This difference was the result of an especially slow performance of the TP and AR subgroups (3.85±1.20 and 3.88±1.46, respectively; p<0.01, compared to the control group). TP was the only subgroup to show an increased tap-to-tap variation at their fastest tapping rate compared to the control group (0.070±0.057 vs. 0.029±0.025 s, respectively, p<0.05). The TP subgroup also showed hastening when they followed an externally given rhythm of 2.5 Hz and they tapped at 2.73±0.36 Hz ( p<0.05). Conclusions. Externally driven and self-paced tapping are preserved in patients with PD, when examined at their best ‘on’ state. The tremor predominant subgroup seems to have specific pacing disturbances.

Ideomotor and Ideational Apraxia in Corticobasal Degeneration: A Case Study

Corticobasal degeneration (CBD) is a progressive disorder that can be characterised by asymmetrical akinetic rigidity, involuntary movements, cortical sensory loss, alien limb syndrome and asymmetrical apraxia (Gibb et al., 1989; Rinnie et al., 1994). Diagnosis of praxic disabilities is thought to be essential for distinguishing CBD, in its early stage, from other akinetic-rigid syndromes. However, the nature of apraxia in CBD, and the relations between ideomotor and ideational apraxia, are not well understood. For example, if there is an ideational deficit in a given patient, does this deficit occur independently of any ideomotor disorder, or are the two impairments linked in some manner? In the present paper we report a case study of a patient with apraxia due to CBD. We examine whether the disorder is confined to production tasks, or whether there is also a related deficit in recognising the correct actions performed with objects (an ideational deficit). We also evaluate whether a disorder found for action with single objects dissociates from the ability to link multiple actions into more complex, everyday tasks. The performance of our patient showed an impairment in both action production and action recognition system, suggesting a component of ideational as well as ideomotor apraxia in CBD.

Apraxia Differs in Corticobasal Degeneration and Left-Parietal Stroke: A Case Study

Corticobasal degeneration (CBD) is a progressive disorder characterized by both cortical and basal ganglia dysfunction such as asymmetrical apraxia, and akinetic rigidity, involuntary movements, and cortical sensory loss. Although apraxia is a key finding for the differential diagnosis of CBD, it has not been determined whether the features of apraxia seen in subjects with CBD are similar to those features exhibited by subjects with left-hemisphere damage from stroke. Therefore, for both clinical purposes and in order to better understand the brain mechanisms that lead to apraxia in CBD, we studied praxis in a patient with CBD and compared him to patients who are apraxic from left-parietal strokes. We used three-dimensional movement analyses to compare the features of apraxic movement. This subject with CBD was a dentist whose initial complaint had been that he “forgot” how to use his tools in the mouths of his patients. Analyses were performed on the trajectories made when using a knife to actually slice bread, and when repetitively gesturing slicing made to verbal command. Movements of the left hand, wrist, elbow, and shoulder were digitized in 3-D space. Although the CBD subject was clearly apraxic, the features of his apraxia differed markedly from those of the subjects with lesions in the left parietal lobe. For movements to command, the CBD subject showed joint coordination deficits, but his wrist trajectories were produced in the appropriate spatial plane, were correctly restricted to a single plane, and, like control subjects, were linear in path shape. However, when he was actually manipulating the tool and object, all of these aspects of his trajectories became impaired. In contrast, the deficits of the apraxic subjects with left-parietal damage were most pronounced to verbal command with their movements improving slightly although remaining impaired during actual tool and object manipulation. Unlike patients with parietal strokes, patients with CBD have degeneration in several systems and perhaps deficits in these other areas may account for the differences in praxic behavior.