The CAM test: a novel tool to quantify the decline in vertical upper limb pointing movements with ageing.

BACKGROUND AND AIM: Although upper limb movements in the vertical plane are very commonly used during the activities of daily life, there is still a lack of a reliable and easy standardized procedure to quantify them. In particular, ageing is associated with a decline in performances of coordinated movements, but a tool to quantify this decline is missing. METHODS: We created a novel portable test called counting arm movement test (CAM test). Participants were asked to perform fast and accurate successive pointing movements towards two fixed targets (mechanical counters) located in a vertical plane in the parasagittal axis during three different time periods (15, 30, 45 s). Each upper limb was assessed separately. The test was evaluated in a group of 63 healthy subjects (mean age ± SD 49.1 ± 19.8 years; F/M 33/30; range 18-87 years). RESULTS: Motor performances (number of clicks) significantly decreased as a function of age for both the dominant side (age effect; linear regression; p < 0.0001 for 15, 30 and 45 s) and the non-dominant side (linear regression; p < 0.0001 for 15, 30 and 45 s). Performances on the dominant and non-dominant side were linearly correlated with the time periods (p < 0.0001 on both sides). The symmetry index (ratio of performance on the dominant side divided by performance on the non-dominant side) was correlated linearly and positively with the duration of the test (y = 0.002x + 1.053; p = 0.0056). We also found a linear relationship between upper limb length and motor performance on the non-dominant side for 15 s (p = 0.023) and 45 s (p = 0.041). The test was characterized by a very high correlation between the results obtained by two investigators during two successive sessions in a subgroup of 7 subjects (Pearson product moment correlation: 0.989 for the dominant side and 0.988 for the non-dominant side). CONCLUSION: The CAM test appears as a robust and low cost tool to quantify upper limb pointing movements. In particular, the test strongly discriminates the effects of age upon motor performances in upper limbs. Future studies are now required to establish the sensitivity, specificity and reliability of this procedure in selected neuromuscular or skeletal diseases affecting the elderly.

Apraxic agraphia following thalamic damage: Three new cases.

Apraxic agraphia (AA) is a so-called peripheral writing disorder following disruption of the skilled movement plans of writing while the central processes that subserve spelling are intact. It has been observed in a variety of etiologically heterogeneous neurological disorders typically associated with lesions located in the language dominant parietal and frontal region. The condition is characterized by a hesitant, incomplete, imprecise or even illegible graphomotor output. Letter formation cannot be attributed to sensorimotor, extrapyramidal or cerebellar dysfunction affecting the writing limb. Detailed clinical, neurocognitive, neurolinguistic and (functional) neuroimaging characteristics of three unique cases are reported that developed AA following a thalamic stroke. In marked contrast to impaired handwriting, non-handwriting skills, such as oral spelling, were hardly impaired. Quantified Tc-99m ECD SPECT consistently showed a decreased perfusion in the anatomoclinically suspected prefrontal regions. The findings suggest crucial involvement of the anterior (and medial) portion of the left thalamus within the neural network subserving the graphomotor system. Functional neuroimaging findings seem to indicate that AA after focal thalamic damage represents a diaschisis phenomenon.

Mindfulness Training among Individuals with Parkinson's Disease: Neurobehavioral Effects.

Objective. To investigate possible neurobehavioral changes secondary to a mindfulness based intervention (MBI) training for individuals living with Parkinson's disease (PD). Background. In the context of complementary medicine, MBIs are increasingly being used for stress reduction and in patient populations coping with chronic illness. The use of alternative and complementary medicine may be higher in patients with chronic conditions such as PD. However, behavioral effects of mindfulness training in PD have not yet been reported in the literature and this points to an unmet need and warrants further examination. Methods. A total of 27 out of 30 PD patients completed a randomized controlled longitudinal trial. Questionnaires and the UPDRS I-IV were obtained at baseline and 8-week follow-up. Results. Significant changes after the MBI were found including a 5.5 point decrease on the UPDRS motor score, an increase of 0.79 points on Parkinson's disease questionnaire (PDQ-39) pain item, and a 3.15 point increase in the Five Facet Mindfulness Questionnaire observe facet. Conclusions. To the best of our knowledge, this is the first quantitative analysis of neurobehavioral effects of MBI in PD.

Apraxic agraphia following bithalamic damage.

OBJECTIVES: Apraxic agraphia (AA) is a peripheral writing disorder generally considered to result from a causative lesion in the parietal and/or prefrontal lobe of the language dominant hemisphere (De Smet, Engelborghs, Paquier, De Deyn, & Mariën, 2011). De Smet et al. (2011), however, confirmed that AA might be associated with lesions outside the typical language areas such as the cerebellum or the thalamus. We report a 32-year-old ambidextrous patient with a left frontal lobectomy who following bilateral thalamic damage developed AA. METHOD: Detailed neurolinguistic and neurocognitive test results were obtained after resection of an extensive left frontal lobe tumour by means of a set of standardised tests. Repeated investigations were performed after a bithalamic stroke. Functional imaging was performed by means of quantified SPECT. RESULTS: Normal neurolinguistic test results were obtained after tumour resection. Neurocognitive test results, however, showed a dysexecutive syndrome and frontal behavioural deficits, including response inhibition. AA occurred after a bithalamic stroke while non-handwriting written language skills, such as typing, were normal. Quantified SPECT showed a significant bifrontal hypoperfusion. CONCLUSION: Neurolinguistic follow-up findings and SPECT evidence in this unique patient with bithalamic damage for the first time indicate that AA in the alphabetic script may result from diaschisis affecting the frontal writing centre. The findings suggest that the thalamus is critically implicated in the neural network subserving graphomotor processing.

Atypical cerebral language dominance in a right-handed patient: An anatomoclinical study.

OBJECTIVE: Approximately 97% of the right-handers has left hemisphere language dominance. Within the language dominant hemisphere Broca's area is of crucial importance for a variety of linguistic functions. As a result, tumour resection in and around Broca's area is controversial. However, studies showed that by means of Direct Electrical Stimulation (DES) tumour resection in this region can be safely performed. We report unexpected anatomoclinical findings in a right-handed patient who underwent tumour resection in the left prefrontal lobe. METHODS: Language functions in this right-handed patient were extensively examined in the pre-, intra-, and postoperative phase by means of a standardised battery of neurolinguistic and neurocognitive tests. Results obtained in the pre- and postoperative phase are compared. In addition, intraoperative DES findings and postoperative functional Magnetic Resonance Imaging (fMRI) and Diffusion Tensor Imaging (DTI) results are reported. RESULTS: Tumour resection near Broca's area was safely performed since no positive language sites were found during intraoperative DES. Since no linguistic deficits occurred in the pre-, intra-, or postoperative phase, atypical language dominance was suspected. Neuropsychological investigations, however, disclosed permanent executive dysfunction. Postoperative fMRI and DTI confirmed right cerebral language dominance as well as a crossed cerebro-cerebellar functional link with the left cerebellar hemisphere. DISCUSSION: Atypical right hemisphere language dominance in this right-handed patient is reflected by: (1) the total absence of language problems in the pre-, intra- and postoperative phase, (2) absence of positive stimulation sites during DES, (3) a clearly more pronounced arcuate fasciculus in the right cerebral hemisphere (DTI), (4) a crossed functional connection between the right cerebrum and the left cerebellum (fMRI). Two hypothetical explanations for the pattern of crossed cerebral language dominance are put forward: (1) preoperative brain plasticity mechanisms inducing a shift of language functions to the right hemisphere or (2) right hemisphere language dominance as a maturational variant. This case with atypical cerebral language dominance shows that although DES is the 'gold standard' to identify eloquent language regions and their pathways, fMRI and DTI are important adjuncts to guide surgery, to identify language lateralisation and to study anatomoclinical correlations.

Mindfulness based intervention in Parkinson's disease leads to structural brain changes on MRI: a randomized controlled longitudinal trial.

OBJECTIVE: The aim of the current study is to investigate structural changes on brain MRI using voxel based morphometry (VBM) related to an eight-week mindfulness based intervention (MBI) in Parkinson's Disease (PD). METHODS: A total of 27 out of 30 PD patients completed a randomized controlled longitudinal trial. Fourteen patients participated in a structured eight-week program of MBI. Thirteen patients received usual care (UC) alone. MRI data sets of the brain were obtained at baseline and after eight weeks follow-up. VBM analysis was performed using DARTEL from the SPM8 software. The resulting difference maps were statistically compared to examine gray matter density (GMD) differences. Results were reported at p<0.001, uncorrected for multiple comparisons. RESULTS: Increased GMD was found in the MBI compared to the UC group in the region of interest (ROI) analysis in the right amygdala, and bilaterally in the hippocampus. Whole brain analysis showed increased GMD in the left and right caudate nucleus, the left occipital lobe at the lingual gyrus and cuneus, the left thalamus, and bilaterally in the temporo-parietal junction. In contrast, GMD differences were found in the UC group in the left anterior lobe and dentate nucleus of the cerebellum. CONCLUSIONS: To the best of our knowledge this is the first quantitative analysis of neurobiological effects of MBI in PD. Increased GMD was found in the MBI group in the neural networks that have been postulated to play an important role in PD. These areas have also been implicated in the functional networks mediating the benefits of meditation.

Spinal cord stimulation modulates cerebral neurobiology: a proton magnetic resonance spectroscopy study.

INTRODUCTION: Although spinal cord stimulation (SCS) is a widely used treatment for chronic neuropathic pain secondary to spinal surgery, little is known about the underlying physiological mechanisms. METHODS: The primary aim of this study is to investigate the neural substrate underlying short-term SCS by means of (1)H MR spectroscopy with short echo time, in 20 patients with failed back surgery syndrome. RESULTS: Marked increase of γ-aminobutyric acid (GABA) and decrease in glucose in the ipsilateral thalamus were found between baseline situation without SCS and after 9' of SCS, indicating the key role of the ipsilateral thalamus as a mediator of chronic neuropathic pain. In addition, this study also showed a progressive decrease in glucose in the ipsilateral thalamus over time, which is in line with the findings of previous studies reporting deactivation in the ipsilateral thalamic region. CONCLUSIONS: The observation of GABA increase and glucose decrease over time in the ipsilateral thalamus may be the causal mechanism of the pain relief due to SCS or an epiphenomenon.

Cognitive, affective and behavioural disturbances following vascular thalamic lesions: a review.

During the last decades, many studies have shown that the thalamus is crucially involved in language and cognition. We critically reviewed a study corpus of 465 patients with vascular thalamic lesions published in the literature since 1980. 42 out of 465 (9%) cases with isolated thalamic lesions allowed further neurocognitive analysis. On the neurolinguistic level, fluent output (=31/33; 93.9%), normal to mild impairment of repetition (=33/35; 94.3%), mild dysarthria (=8/9; 88.9%) and normal to mild impairment of auditory comprehension (=27/34; 79.4%) were most commonly found in the group of patients with left and bilateral thalamic lesions. The taxonomic label of thalamic aphasia applied to the majority of the patients with left thalamic damage (=7/11; 63.6%) and to one patient with bithalamic lesions (=1/1). On the neuropsychological level, almost 90% of the left thalamic and bithalamic patient group presented with amnestic problems, executive dysfunctions and behaviour and/or mood alterations. In addition, two thirds (2/3) of the patients with bilateral thalamic damage presented with a typical cluster of neurocognitive disturbances consisting of constructional apraxia, anosognosia, desorientation, global intellectual dysfunctioning, amnesia, and executive dysfunctions associated with behaviour and/or mood alterations. Our study supports the long-standing view of a 'lateralised linguistic thalamus' but restates the issue of a 'lateralised cognitive thalamus'. In addition, critical analysis of the available literature supports the view that aphasia following left or bithalamic damage constitutes a prototypical linguistic syndrome.

Crossed aphasia and visuo-spatial neglect following a right thalamic stroke: a case study and review of the literature.

Crossed aphasia in dextrals (CAD) following pure subcortical lesions is rare. This study describes a right-handed patient with an ischemic lesion in the right thalamus. In the post-acute phase of the stroke, a unique combination of 'crossed thalamic aphasia' was found with left visuo-spatial neglect and constructional apraxia. On the basis of the criteria used in Mariën et al. [67], this case-report is the first reliable representative of vascular CAD following an isolated lesion in the right thalamus. Furthermore, this paper presents a detailed analysis of linguistic and cognitive impairments of 'possible' and 'reliable' subcortical CAD-cases published since 1975. Out of 25 patients with a pure subcortical lesion, nine cases were considered as 'possibly reliable or reliable'. A review of these cases reveals that: 1) demographic data are consistent with the general findings for the entire group of vascular CAD, 2) the neurolinguistic findings do not support the data in the general CAD-population with regard to a) the high prevalence of transcortical aphasia and b) the tendency towards a copresence of an oral versus written language dissociation and a 'mirror-image' lesion-aphasia profile, 3) subcortical CAD is not a transient phenomenon, 4) the lesion-aphasia correlations are not congruent with the high incidence of anomalous cases in the general CAD-population, 5) neuropsychological impairments may accompany subcortical CAD.

Disrupted auto-activation, dysexecutive and confabulating syndrome following bilateral thalamic and right putaminal stroke.

OBJECTIVE: Clinical, neuropsychological, structural and functional neuroimaging results are reported in a patient who developed a unique combination of symptoms after a bi-thalamic and right putaminal stroke. The symptoms consisted of dysexecutive disturbances associated with confabulating behavior and auto-activation deficits. BACKGROUND: Basal ganglia and thalamic lesions may result in a variety of motor, sensory, neuropsychological and behavioral syndromes. However, the combination of a dysexecutive syndrome complicated at the behavioral level with an auto-activation and confabulatory syndrome has never been reported. METHODS: Besides clinical and neuroradiological investigations, an extensive set of standardized neuropsychological tests was carried out. RESULTS: In the post-acute phase of the stroke, a dysexecutive syndrome was found in association with confabulating behavior and auto-activation deficits. MRI showed focal destruction of both thalami and the right putamen. Quantified ECD SPECT revealed bilateral hypoperfusions in the basal ganglia and thalamus but no perfusion deficits were found at the cortical level. CONCLUSION: The combination of disrupted auto-activation, dysexecutive and confabulating syndrome in a single patient following isolated subcortical damage renders this case exceptional. Although these findings do not reveal a functional disruption of the striato-ventral pallidal-thalamic-frontomesial limbic circuitry, they add to the understanding of the functional role of the basal ganglia in cognitive and behavioral syndromes.

Impairment of syntax and lexical semantics in a patient with bilateral paramedian thalamic infarction.

Bilateral vascular thalamic lesions are rare. Although a variety of neurobehavioral manifestations have been described, the literature is less documented with regard to accompanying linguistic disturbances. This article presents an in-depth neurolinguistic analysis of the language symptoms of a patient who incurred bilateral paramedian ischemic damage of the thalamus. In the post-acute phase of the stroke, a unique combination of transcortical sensory aphasia with syntactic impairment was found. Because of this atypical semiological association, additional analyses of spontaneous speech were performed. In spite of the typological affinity with the grammatic characteristic of marked simplification of syntax observed in Broca's aphasia, only a wordclass specific, lexical-semantic deficit for verbs was objectified. The hypothesis that lexical-semantic disturbances in our patient might result from a functional deafferentiation of both thalami with the frontal lobe is supported by: (1) associated neuropsychological deficits of frontal origin and (2) frontal-like behavioral disturbances.

Pathophysiology of language switching and mixing in an early bilingual child with subcortical aphasia.

Acquired aphasia after circumscribed vascular subcortical lesions has not been reported in bilingual children. We report clinical and neuroimaging findings in an early bilingual boy who incurred equally severe transcortical sensory aphasia in his first language (L1) and second language (L2) after a posterior left thalamic hemorrhage. Following recurrent bleeding of the lesion the aphasic symptoms substantially aggravated. Spontaneous pathological language switching and mixing were found in both languages. Remission of these phenomena was reflected on brain perfusion SPECT revealing improved perfusion in the left frontal lobe and left caudate nucleus. The parallelism between the evolution of language symptoms and the SPECT findings may demonstrate that a subcortical left frontal lobe circuity is crucially involved in language switching and mixing.