Anamarli Nucci

Prospective neuroimaging study in hereditary spastic paraplegia with thin corpus callosum.

Our objective was to estimate the frequency as well as to establish the clinical and neuroimaging profile of hereditary spastic paraplegia with thin corpus callosum (HSP‐TCC). HSP‐TCC was recognized as a specific clinical subtype of HSP and mapped to chromosome (ch) 15q13‐15 in Japanese families. It has been considered rare in western countries. We assessed 45 patients with autosomal recessive HSP from 20 different families in search of clinical and imaging criteria for the diagnosis of HSP‐TCC. In addition, HSP‐TCC patients underwent further neurological, imaging and genetic evaluation. MRI scans were performed in a 2T scanner and sagittal T1 weighted images used for semiautomated volumetric measurements of corpus callosum, cerebellum, and brain. In seven patients, a 2‐year follow‐up MRI scan was performed. We genotyped seven microsatellite markers flanking the 15q13‐15 candidate region and calculated two‐point and multipoint LOD scores (Z). We identified 13 patients from seven unrelated families with HSP‐TCC. MRI showed significant corpus callosum, cerebral and cerebellar volumetric reductions (P < 0.001, P = 0.03, and P = 0.01, respectively). In the prospective analysis, we found progressive corpus callosum atrophy (P = 0.04). Two‐point and multipoint LOD scores were significantly negative for markers genotyped on ch 15q. However, independent pedigree analysis did not yield significant results. HSP‐TCC was found in 35% of families with autosomal recessive HSP. MRI volumetry showed cerebral and cerebellar atrophy in association with progressive corpus callosum thinning. Genetic studies did not show evidence for linkage to ch 15q.

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.

Electrophysiological evaluation in myotonic dystrophy: correlation with CTG length expansion

In myotonic dystrophy (MD), disease severity has been correlated with expansion of CTG repeats in chromosome 19. The aims of this study were to evaluate efficacy of electromyography in the diagnosis of MD, access the frequency and the characteristics of peripheral involvement in the disease and to verify whether the CTG repeats correlated with the electrophysiological abnormalities. Twenty-five patients and six relatives at risk of carrying the MD gene were examined. Electrical myotonia (EM) was scored. Sensory and motor conduction velocity (CV) were studied in five nerves. Leukocyte DNA analysis was done in 26 subjects. Myopathy and myotonia were found in 27 cases. EM was most frequent in muscles of hand and in tibialis anterior. No significant correlation was found between EM scores and length of CTG expansions. EM scores correlated significantly with the degree of clinical myopathy, expressed by a muscular disability scale. Peripheral neuropathy was found in eight subjects and was not restricted to those who were diabetics.

Sensory Neuronopathy and Autoimmune Diseases

Sensory neuronopathies (SNs) are a specific subgroup of peripheral nervous system diseases characterized by primary degeneration of dorsal root ganglia and their projections. Multifocal sensory symptoms often associated to ataxia are the classical features of SN. Several different etiologies have been described for SNs, but immune-mediated damage plays a key role in most cases. SN may herald the onset of some systemic autoimmune diseases, which further emphasizes how important the recognition of SN is in clinical practice. We have thus reviewed available clinical, neurophysiological, and therapeutic data on autoimmune disease-related SN, namely, in patients with Sjögrens syndrome, autoimmune hepatitis, and celiac disease.

Progression of ataxia in patients with Machado-Joseph disease†

Although ataxia is the most distressing manifestation of Machado‐Joseph disease (MJD), little is known about its natural history. Therefore, we prospectively followed a cohort of patients with MJD for 13 months to characterize the progression of ataxia and identify its contributory factors. The international cooperative ataxia rating scale (ICARS) was used to estimate severity of ataxia at baseline and at follow‐up. Thirty‐four patients were enrolled in the study, 22 of whom were men. Mean age at onset of the disease was 34.7 years and length of expanded CAG repeat was 66. Mean ICARS scores at baseline was 37.6 and at follow‐up was 42.7 (P < 0.001). Multivariate analysis did not find significant association of progression of disease and age at disease onset, length of expanded (CAG), or duration of disease.

Spinal cord atrophy correlates with disease duration and severity in amyotrophic lateral sclerosis.

Abstract Our objective was to investigate spinal cord (SC) atrophy in amyotrophic lateral sclerosis (ALS) patients, and to determine whether it correlates with clinical parameters. Forty-three patients with ALS (25 males) and 43 age- and gender-matched healthy controls underwent MRI on a 3T scanner. We used T1-weighted 3D images covering the whole brain and the cervical SC to estimate cervical SC area and eccentricity at C2/C3 level using validated software (SpineSeg). Disease severity was quantified with the ALSFRS-R and ALS Severity scores. SC areas of patients and controls were compared with a Mann-Whitney test. We used linear regression to investigate association between SC area and clinical parameters. Results showed that mean age of patients and disease duration were 53.1 ± 12.2 years and 34.0 ± 29.8 months, respectively. The two groups were significantly different regarding SC areas (67.8 ± 6.8 mm² vs. 59.5 ± 8.4 mm², p < 0.001). Eccentricity values were similar in both groups (p = 0.394). SC areas correlated with disease duration (r = − 0.585, p < 0.001), ALSFRS-R score (r = 0.309, p = 0.044) and ALS Severity scale (r = 0.347, p = 0.022). In conclusion, patients with ALS have SC atrophy, but no flattening. In addition, SC areas correlated with disease duration and functional status. These data suggest that quantitative MRI of the SC may be a useful biomarker in the disease.

Brain tumor-like lesion in Behçet disease.

We report a patient with longstanding Behçet disease who presented sudden onset of headache and facial paresis. The magnetic resonance imaging (MRI) showed a mass in the right thalamus, extending to the lentiform nucleus, subthalamic area, right cerebral peduncle and deep subcortical white matter. Stereotactic brain biopsy disclosed gliosis with no signs of malignancy. The diagnosis of a pseudotumoral form of neuro-Behçet disease was done and she was treated with pulse methylpredinisolone and intravenous cyclophosphamide. After 8 weeks she had improved and a new MRI showed disappearance of the tumor-like lesion. The differential diagnosis, especially with central nervous system tumor is emphasized.

Amyotrophic lateral sclerosis: combined nutritional, respiratory and functional assessment

OBJECTIVE To establish correlations between nutritional, functional and respiratory indices of patients with amyotrophic lateral sclerosis (ALS). METHOD Twenty patients (13 appendicular-GA and 7 bulbar-GB) were included in the multidisciplinary study at the Neurological Clinic Ambulatory of the University of Campinas Hospital. RESULTS Among the GA type significant correlation was observed between maximal inspiratory (MIP) and expiratory (MEP) pressure (r=-0.76), MEP and pulse oxymetry (r=0.58), MIP and percent weight loss (%WL; r=0.59), and between MIP, total and subscale respiratory scores (ALSFRS-R) with %WL. With regard to the GB, correlation was found between MEP and body mass index (BMI) (r=0.97). In both GA and GB correlations were noticed between the BMI and the variables mass (kg), fat (%), arm and wrist circumference (cm), and tricipital, subscapular and supra-iliac skinfolds (mm), as well as the arm muscle circumference (cm) and fatty arm muscular area (mm2). CONCLUSION It is suggested that the application of simple anthropometric measurements could be useful in routine monitoring of patients with ALS.

Prospective study of peripheral neuropathy in Machado–Joseph disease

Peripheral neuropathy (PN) has long been recognized in Machado–Joseph disease (MJD), but its natural history is an unsettled issue. Therefore, we prospectively assessed 40 with MJD for 13 months with nerve conduction (NC) studies and the revised total neuropathy score (TNSr) to study the progression of PN. There was no significant change in the TNSr score over the follow‐up period. In contrast, the average sural sensory nerve action potential (SNAP) amplitude decreased significantly over the same interval from a mean of 13.2 μV to 9.8 μV (P < 0.001). There was an inverse correlation between the change in the sural SNAP amplitude and the length of the CAG triplet repeat expansion (r = 0.574, P < 0.001). The reduction in the mean sural SNAP amplitude also correlated with progression of ataxia. This indicates that PN progresses faster in individuals with larger (CAG)n expansions, and nerve conduction studies may be useful to study disease progression in MJD. Muscle Nerve, 2009