Anelyssa D’Abreu

Sleep symptoms and their clinical correlates in Machado–Joseph disease

Objective –  To evaluate the presence of sleep symptoms in Machado–Joseph disease/spinocerebellar ataxia type 3 (MJD/SCA3).

Muscle Excitability Abnormalities in Machado-Joseph Disease

OBJECTIVES To estimate the frequency of and to characterize muscle excitability abnormalities in Machado-Joseph disease (MJD). DESIGN Machado-Joseph disease is a common autosomal dominant cerebellar ataxia caused by an unstable CAG trinucleotide repeat expansion. Muscle cramps and fasciculations are frequent and sometimes disabling manifestations. However, their frequency and pathophysiological mechanisms remain largely unknown. Symptomatic patients with MJD (hereinafter MJD patients) with molecular confirmation were assessed prospectively. A standard questionnaire addressing clinical features of muscle cramps and fasciculations was used. The Cramps Disability Scale was used to quantify cramps-related disability. Patients underwent neurophysiological testing with routine techniques. F waves of the right median nerves were obtained, and persistence indexes were calculated. Four muscles (deltoid, first dorsal interossei, tibialis anterior, and vastus lateralis) were examined by needle electromyography. A semiquantitative scale (from 0 [no activity] to 4 [continuous activity]) was used to determine the frequency of rest fasciculations in each muscle. RESULTS Fifty MJD patients (29 men) were included in the study. Their mean age at examination was 46.3 years, their mean age at onset of the disease was 35 years, and the mean duration of disease was 11.2 years. Abnormal CAG(n) varied from 59 to 75 repeats. Forty-one patients presented with muscle cramps; in 10, this was their first symptom. The frequency of cramps varied between 1 and 90 episodes a week. For 15 patients, cramps were the chief complaint, frequently disturbing sleep or work (Cramps Disability Scale score, 2 or 3). Lower limbs were affected in 37 individuals, but unusual regions, such as the face and abdominal muscles, were also involved. Fasciculations were found in 25 individuals; in 8 patients, they included facial muscles. However, fasciculations were not a significant complaint for any of these patients. The clinical and neurophysiological profile of MJD patients with and without cramps was not significantly different. However, MJD patients with fasciculations had more severe damage to their peripheral nerves. CONCLUSIONS Muscle excitability abnormalities were found in 41 MJD patients (82%), and they were the presenting complaint in 10 (20%). They are related to altered excitability of peripheral motor axons, but mechanisms underlying cramps and fasciculations are possibly distinct in MJD patients.

MRI-texture analysis of corpus callosum, thalamus, putamen, and caudate in Machado-Joseph disease.

Texture analysis (TA) is a branch of image processing, which attempts to convey “texture” information from digital images, such as magnetic resonance images (MRI). Machado‐Joseph disease (MJD) affects mainly cerebellum and brainstem, but recent studies have shown that other cerebral structures may also be affected.

Glucocerebrosidase gene variants in parkinsonian patients with Machado Joseph/spinocerebellar ataxia 3

UNLABELLED Machado-Joseph disease/spinocerebellar ataxia type 3 (MJD/SCA3) may rarely presents a parkinsonian phenotype. Considering that mutations in the glucocerebrosidase (GBA) gene have been associated with Parkinson disease, we investigated whether these would be more prevalent in MJD/SCA3 patients with parkinsonian manifestations than in those without them. METHODS MJD/SCA3 patients with parkinsonian features were identified and compared to relatives and to a MJD/SCA3 control group with no such features. The GBA gene was sequenced and, in a subset of patients and in normal volunteers, GBA enzyme activity was measured. RESULTS We have identified nine index MJD/SCA3 patients with parkinsonian manifestations. Overall, GBA sequence variations were found in 3/9 MJD/SCA3 index cases with parkinsonian manifestations (33%) and in 0/40 MJD/SCA3 controls without parkinsonism (p=0.03, Fisher exact test). The GBA sequence variations found were p.K(-27)R, p.E326K, and p.T369M. The latter two sequence variations were also found in two symptomatic relatives with no parkinsonian manifestations. A MJD/SCA3 relative belonging to the first positive pedigree and carrier of the p.K(-27)R mutation also presented parkinsonian manifestations. GBA activity in MJD/SCA3 patients was similar to those found in the normal control group. CONCLUSION Sequence variations at the GBA gene may play a role as a minor, modifying gene of MJD/SCA3 phenotype. This hypothetical role was not related to changes in GBA activity in peripheral leukocytes.

Thalamic volume and dystonia in Machado-Joseph disease.

Neuropathological studies and one positron emission tomography study demonstrated involvement of the thalamus in Machado–Joseph disease (MJD), but a large series of patients has not been studied. Our objective was to perform an automated and a manual segmentation of the thalamus in patients with MJD.

Diffuse Decreased Gray Matter in Patients with Idiopathic Craniocervical Dystonia: A Voxel-Based Morphometry Study

Background: Recent studies have addressed the role of structures other than the basal ganglia in the pathophysiology of craniocervical dystonia (CCD). Neuroimaging studies have attempted to identify structural abnormalities in CCD but a clear pattern of alteration has not been established. We performed whole-brain evaluation using voxel-based morphometry (VBM) to identify patterns of gray matter (GM) changes in CCD. Methods: We compared 27 patients with CCD matched in age and gender to 54 healthy controls. VBM was used to compare GM volumes. We created a two-sample t-test corrected for subjects’ age, and we tested with a level of significance of p < 0.001 and false discovery rate (FDR) correction (p < 0.05). Results: Voxel-based morphometry demonstrated significant reductions of GM using p < 0.001 in the cerebellar vermis IV/V, bilaterally in the superior frontal gyrus, precuneus, anterior cingulate and paracingulate, insular cortex, lingual gyrus, and calcarine fissure; in the left hemisphere in the supplementary motor area, inferior frontal gyrus, inferior parietal gyrus, temporal pole, supramarginal gyrus, rolandic operculum, hippocampus, middle occipital gyrus, cerebellar lobules IV/V, superior, and middle temporal gyri; in the right hemisphere, the middle cingulate and precentral gyrus. Our study did not report any significant result using the FDR correction. We also detected correlations between GM volume and age, disease duration, duration of botulinum toxin treatment, and the Marsden–Fahn dystonia scale scores. Conclusion: We detected large clusters of GM changes chiefly in structures primarily involved in sensorimotor integration, motor planning, visuospatial function, and emotional processing.

Clinical correlates of autonomic dysfunction in patients with Machado-Joseph disease

França Jr MC, D’Abreu A, Nucci A, Lopes‐Cendes I. Clinical correlates of autonomic dysfunction in patients with Machado‐Joseph disease.
Acta Neurol Scand: 2010: 121: 422–425.
© 2010 The Authors Journal compilation

Pattern of Reduced Functional Connectivity and Structural Abnormalities in Parkinson’s Disease: An Exploratory Study

Background MRI brain changes in Parkinson’s disease (PD) are controversial. Objectives We aimed to describe structural and functional changes in PD. Methods Sixty-six patients with PD (57.94 ± 10.25 years) diagnosed according to the UK Brain Bank criteria were included. We performed a whole brain analysis using voxel-based morphometry (VBM–SPM 8 software), cortical thickness (CT) using CIVET, and resting-state fMRI using the Neuroimaging Analysis Kit software to compare patients and controls. For VBM and CT we classified subjects into three groups according to disease severity: mild PD [Hoehn and Yahr scale (HY) 1–1.5], moderate PD (HY 2–2.5), and severe PD (HY 3–5). Results We observed gray matter atrophy in the insula and inferior frontal gyrus in the moderate PD and in the insula, frontal gyrus, putamen, cingulated, and paracingulate gyri in the severe groups. In the CT analysis, in mild PD, cortical thinning was restricted to the superior temporal gyrus, gyrus rectus, and olfactory cortex; in the moderate group, the postcentral gyrus, supplementary motor area, and inferior frontal gyrus were also affected; in the severe PD, areas such as the precentral and postentral gyrus, temporal pole, fusiform, and occipital gyrus had reduced cortical thinning. We observed altered connectivity at the default mode, visual, sensorimotor, and cerebellar networks. Conclusion Subjects with mild symptoms already have cortical involvement; however, further cerebral involvement seems to follow Braak’s proposed mechanism. Similar regions are affected both structurally and functionally. We believe the combination of different MRI techniques may be useful in evaluating progressive brain involvement and they may eventually be used as surrogate markers of disease progression.

Clinical predictors of cognitive impairment and psychiatric complications in Parkinson's disease.

OBJECTIVE To estimate the clinical and demographics aspects that may contribute to cognitive impairment and psychiatric symptoms in Parkinsons disease (PD). METHOD All patients answered a structured standardized clinical questionnaire. Two movement disorders specialists performed the following scale: Unified Parkinsons disease rating score (UPDRS), the modified Hoehn and Yahr staging, Schwab and England Scale, SCOPA cognition (SCOPA-COG), SCOPA-Psychiatric complications (SCOPA-PC) and Non-Motor Symptoms Scale (NMSS). We built a generalized linear model to assess predictors for the SCOPA-COG and SCOPA-PC scores. RESULTS Almost 37% of our patients were demented as per SCOPA-COG scores. Level of education and the UPDRS-Subscale III were predictors of cognitive impairment. Higher scores in domain 3 of NMSS and male gender were associated with psychiatric complications as assessed per the SCOPA-PC. CONCLUSION Level of education and disease severity are predictors of dementia in PD. Psychiatric complications are more commonly observed in men.

Misdiagnosis of hemifacial spasm is a frequent event in the primary care setting

UNLABELLED Primary hemifacial spasm (HFS) is characterized by irregular and involuntary contraction of the muscles innervated by the ipsilateral facial nerve. Treatment controls symptoms and improves quality of life (QoL). OBJECTIVE Evaluate the initial diagnosis and treatment of HFS prior to referral to a tertiary center. METHOD We interviewed through a standard questionnaire 66 patients currently followed in our center. RESULTS Mean age: 64.19±11.6 years, mean age of symptoms onset: 51.9±12.5 years, male/female ratio of 1:3. None of the patients had a correct diagnosis in their primary care evaluation. Medication was prescribed to 56.8%. Mean time from symptom onset to botulinum toxin treatment: 4.34 ±7.1 years, with a 95% satisfaction. Thirty percent presented social embarrassment due to HFS. CONCLUSION Despite its relatively straightforward diagnosis, all patients had an incorrect diagnosis and treatment on their first evaluation. HFS brings social impairment and the delay in adequate treatment negatively impacts QoL.