Visual attention in children with migraine: a controlled comparative study.

The aim of this study was to evaluate the visual attention of children with migraine and compare it with a control group. Thirty migrainous children and 30 controls without headache were subjected to a visual attention assessment with Trail Making Tests (TMT) A/B, Letter Cancellation Test, and the Brazilian computerized test Visual Attention Test, third edition. The migraine group was evaluated after 2 days without headache. The migraine group had an inferior performance compared with the control group on TMT A (P = 0.03) and B (P = 0.001), and more errors on tasks 1 (P = 0.032) and 2 (P = 0.015) of the Visual Attention Test, presenting difficulty with selective and alternate attention. Attention is a neurological function that depends on structures such as the brainstem, cerebral cortex and the limbic system and on neurotransmitters such as dopamine and noradrenaline. The neurochemical aspects involved in the physiopathology of migraine and attention mechanisms probably predispose these children to visual attention deficits.

Mitochondrial encephalomyopathy and hypoparathyroidism associated with a duplication and a deletion of mitochondrial deoxyribonucleic acid.

Diabetes mellitus is the most frequent endocrinopathy associated with mitochondrial disorders, particularly in patients with duplications of mitochondrial DNA (mtDNA). Although hypoparathyroidism has also been described in mitochondrial diseases, there have been few molecular studies in these cases, most of which identified the presence of single mtDNA deletions in the patients' tissues. We studied muscle DNA of a 12-yr-old patient with incomplete Kearns-Sayre syndrome and hypoparathyroidism. Southern analysis showed that muscle DNA contained three populations of mtDNA: wild type (26%), deleted (65%), and duplicated (9%). To determine the sequence of the breakpoint region from deleted and duplicated mtDNA independently, we isolated the deleted and duplicated mtDNA by gel fractionation of a PstI-digested total DNA. The breakpoint was located at mtDNA positions 5788 and 15,448 for both duplicated and deleted molecules. Our study reinforces the concept that endocrinopathies other than diabetes can be associated with a duplication of mtDNA and gives additional support to the hypothesis that the duplication and deletion of mtDNA are generated from the same recombination event.

McArdle's disease in two generations: autosomal recessive transmission with manifesting heterozygote.

A 17-year-old boy had exercise-induced cramps and myoglobinuria. The mother had myalgia and weakness after exercise but the father was asymptomatic. Muscle biopsy was normal in the father but showed glycogen storage and absent or markedly decreased histochemical stain for phosphorylase in mother and son. Autosomal dominant McArdle's disease was considered likely, but biochemical studies showed that muscle phosphorylase activity was 0.6% of normal in the son, 20% in the mother, and 45% in the father, with corresponding decreases of cross-reacting material by immunotitration. These data suggest autosomal recessive transmission. One of the parents was clinically silent and the other was a manifesting heterozygote.

Twenty-five years of HTLV type II follow-up with a possible case of tropical spastic paraparesis in the Kayapo, a Brazilian Indian tribe.

A longitudinal study, spanning 25 years and great demographic and cultural change, found a persistently high prevalence of human T-lymphotropic virus type II (HTLV-II) in the Xikrin Kayapo Indians of Brazil. More than 10% of the children continue to develop immune reactions to the virus in infancy, a sharp increase in seroprevalence occurs between ages 15 and 30 years, and prevalence in older woman still approaches 100%. This suggests that the major modes of transmission (breast milk and sexual activity) have not changed. The demonstration of stable maintenance of HTLV-II in one ethnic group makes migration theories of its dispersal more plausible. However, the infection may not be a negligible burden on population survival: at least 1 of 62 persons followed until age 40 years died of possible tropical spastic paraparesis (TSP).

Duchenne muscular dystrophy in a girl with an (X;15) translocation.

This is a report of a girl with Duchenne muscular dystrophy (DMD) associated with an 46,X,t (X;15) (p21; q 26) chromosome constitution. Although in the eight published cases of girls with DMD and a t(X;aut) different autosomes were involved in the translocation, the breakpoint was always at Xp21. The present case supports the hypothesis that the DMD gene must be located at Xp21. In this study, involvement of the father's chromosomes in the translocation was detected.

Selectivity of human T lymphotropic virus type-1 (HTLV-1) and HTLV-2 infection among different populations in Brazil.

A seroprevalence study for human T lymphotropic virus type-1 (HTLV-1) and HTLV-2 was conducted in Sao Paulo, Brazil among 2,312 individuals that included following groups: 1,148 volunteer blood donors, 37 patients with tropical spastic paraparesis (TSP), 53 with lymphoproliferative disorders, 171 with a history of multiple blood transfusions, 268 human immunodeficiency virus type-1 (HIV-1) seropositive subjects, and 635 Amazonian Indians. Antibodies to HTLV-1/2 were screened by enzyme-linked immunosorbent assay (ELISA) and confirmed by Western blot and/or radioimmunoprecipitation. The differentiation of HTLV-1 and HTLV-2 was achieved using a synthetic recombinant peptide (rgp46) ELISA. We confirmed the presence of HTLV-1 infection in Brazil, both in blood donors (0.4%) and in patients exposed to blood transfusions (2.9%), as well as the occurrence of HTLV-1-associated TSP (11 patients, or 30% of all TSP cases) and adult T cell leukemia/lymphoma (two cases, or 3.5% of all hematologic malignancies). The HIV-1 infected individuals were shown to be coinfected (8.9%) with either HTLV-1 or HTLV-2. All HIV-1 and HTLV-2 coinfected individuals were intravenous drug abusers. In addition, we also demonstrated the presence of HTLV-2 (4.7%), and HTLV-1/2 (0.8%) in tribes of Amazonian Indians who lived in the eastern Amazon basin (southeastern State of Para). The selectivity of these retroviral infections in particular groups is emphasized, as well as the need for HTLV-1/2 screening of all blood donors in Brazil as a public health measure.

Centronuclear myopathy: clinical aspects of ten Brazilian patients with childhood onset.

We herein present 10 patients with the childhood onset form of centronuclear myopathy. All patients underwent a clinical and neurologic examination, and EMG/NVC. A series of ancillary examinations, consisting of muscle enzymes, EEG, EKG, echocardiogram, pulmonary function tests and head CT scan was done in most. The mean age was 16.3 years (3-25). Seven were female. There was no family history in seven and in two it was suggestive of an autosomal recessive inheritance. One patient was adopted and no history was available. Frequent gestational and neonatal abnormalities were present, namely poor fetal movements, maternal polyhydramnios, perinatal hypoxia, hypotonia at birth, and weak crying and feeding. In seven patients there was delayed motor milestones. In most patients the motor involvement was stable or slowly progressive. Upon examination the facies were myopathic and there was a global skeletal muscle involvement in all patients, with muscular hypotonia, atrophy, and areflexia. Characteristically, patients presented with ophthalmoparesis, and weakness of masticatory and facial muscles. We frequently found osteoskeletal abnormalities, namely kyphoscoliosis, tendon retractions and high-arched palate. A restrictive pulmonary function pattern was found in five patients, but only one had a cor pulmonale. CK was abnormally high in one patient, and normal in all others. EMG/NVC disclosed a myopathic pattern in nine; in three there was a mixed neurogenic picture; and in one we found myotonic discharges. A long follow-up (median 8.1 years) showed that only the patient with cor pulmonale had an unfavorable prognosis.

Mitochondrial DNA defects in Brazilian patients with chronic progressive external ophthalmoplegia.

We report herein on eleven Brazilian patients with mitochondrial DNA (mtDNA) deletions, found among thirteen patients with chronic progressive external ophthalmoplegia (CPEO) and ragged-red fibers (RRF). The molecular data was correlated with the morphological and clinical findings. The muscle biopsies were studied by histochemistry, immunohistochemistry and DNA analysis. Muscle mtDNA deletions were mapped and quantitated by Southern blot analysis, polymerase chain reaction and sequencing. Of the eleven patients, ten had CPEO without multisystemic involvement and one had Kearns-Sayre syndrome. Three patients had multiple deletions, two of them with no apparent family history. Eight patients showed heteroplasmic single deletions, ranging in length from 2309 to 7566 bp; three of them had the same 'common deletion' of 4977 bp. The proportion of deleted mtDNA ranged from 14 to 89%. Immunohistochemical studies revealed decreased reactivity with the mtDNA-encoded subunit II of cytochrome c oxidase (COX) in all patients, but preserved activity with the nuclear-encoded COX subunit IV in COX-deficient fibers. Two cases presented a few COX-negative fibers with reduced COX IV immunostaining. We found a high frequency of mtDNA deletions in Brazilian patients with CPEO. There was no correlation between clinical severity, morphological findings and the size or amount of the mutated mtDNA in muscle, suggesting that there are still unknown factors influencing the disease phenotype.

High-dose methotrexate for non-AIDS primary central nervous system lymphoma. Report of 13 cases.

Thirteen patients with primary lymphoma of the central nervous system (CNS) were treated with high-dose intravenous methotrexate (MTX), 3.5 gm/sq m, followed by calcium leucovorin rescue, at 3-week intervals, for three cycles. Eleven patients subsequently received radiation therapy to the whole brain, 30 to 44 Gy. Before radiation therapy, eight patients responded completely and four partially; there was one non-responder. The median Karnofsky score before high-dose MTX therapy was 60 and increased to 90 after treatment. Five of the eight complete responders reached a Karnofsky rating of 100. The three longest responders (one of whom received MTX only) were without recurrence of their disease at 29+, 32, and 32+ months posttherapy. The median response period is 9+ months. The median survival time from the date of the first MTX treatment is 9+ months, and the three longest survival times are 29+, 32+, and 54+ months. All patients received corticosteroids in either unchanging or diminishing dosages during therapy. It is concluded that primary CNS lymphoma is sensitive to high-dose MTX, which provides a safe and easily administered adjuvant to radiation therapy for this neoplasm.

Oxidative phosphorylation dysfunction does not increase the rate of accumulation of age-related mtDNA deletions in skeletal muscle.

Several reports described an age-related accumulation of a particular mitochondrial DNA (mtDNA) deletion ('common deletion') in post-mitotic tissues. These findings led to the hypothesis that free radicals generated inside the mitochondria could damage mtDNA during a normal life span. The impaired electron transfer function resulting from mtDNA damage would increase the production of free radicals creating a vicious cycle. If this vicious cycle is an important player in the somatic accumulation of mtDNA deletions, patients with impaired oxidative phosphorylation (regardless of the primary defect) should have an accelerated accumulation of mtDNA deletions. We tested this hypothesis by performing three analyses: (a) comparing the amounts of the mtDNA 'common deletion' in normal controls and patients with genetically characterized mitochondrial disorders associated with pathogenic mtDNA point mutations or deletions other than the common deletion; (b) analyzing the co-segregation of the age-related mtDNA common deletion with a pathogenic mtDNA point mutation; and (c) by the detection of multiple mtDNA deletions by long PCR in controls and patients with mitochondrial disorders. We observed a positive correlation between age and common deletion levels in controls (r = 0.80) and patients (r = 0.69). The slopes of the curves were similar, suggesting that the rate of accumulation of the age-related common deletion was the same in both groups. We could not find a co-segregation of the pathogenic point mutated mtDNA molecules with the common deletion nor increased number of age-related deletions in patients. Our data do not support the hypothesis that a vicious cycle (damage to mtDNA would affect the respiratory function, leading to the generation of more free radicals, which in turn would provoke additional mtDNA damage) is an important factor in the accumulation of age-related mtDNA deletions.

Temporomandibular joint involvement in a patient with centronuclear myopathy.

We describe here the temporomandibular joint and masticatory muscle abnormalities disclosed by computed tomography and magnetic resonance imaging in a 25-year-old man with centronuclear myopathy (a congenital myopathy) who presented with marked limitation of jaw movements. We found an intense and general fatty replacement of the masticatory muscles, and magnetic resonance imaging signals indicated articular fibrosis. We conclude that in centronuclear myopathy, the presence of weakness and hypomotility of the masticatory muscles can induce chronic abnormalities of the temporomandibular joint.

[The involvement of the brachial plexus in cardiac surgery with median sternotomy for the revascularization of the myocardium: clinical evaluation]. / Comprometimento do plexo braquial na cirurgia cardíaca para revascularização do miocárdio por esternotomia mediana. Avaliação clínica.

To evaluate the involvement of brachial plexus in cardiac surgery with median sternotomy for the revascularization of the myocardium 113 patients (87 men and 26 women) were clinically examined in the preoperative and between the fifth and eight post-operative days. The internal thoracic artery was used in 65 of the 113 patients. The electroneuromyography was not effected in any of the patients. A lesion of the brachial plexus was found in three patients though the internal thoracic artery was used in only one patient. We believe that factors such as posture of the patient, hypothermia, thoracic braces and use of the internal thoracic artery are relevant in the lesions. Hence one must be attentive to all the factors mentioned above so as to avoid or minimize the lesions.

Malaria and stroke. Case report.

Malaria is a parasitic disease with high prevalence in several regions of the world. Infestation by Plasmodium faciparum can, in some cases, affect the central nervous system producing encephalitis resulting in death or neurological sequelae. The mechanisms involved in the pathophysiology of the cerebral lesion are not totally clear and there are currently two theories (mechanical and humoral) concerning this. We report a case of malaria with an atypical evolution, with a stroke lesion in the territory of the middle cerebral artery, with no association with encephalitis. We conclude that the mechanical theory is the one applicable to this patient.

[Periodic paralysis. Clinical analysis in 20 patients]. / Paralisia periódica. Análise clínica de 20 pacientes.

Twenty patients with periodic paralysis were evaluated and the aspects studied included epidemiological data, clinical manifestations, ancillary tests, treatment and evolution. Sixteen patients had the hypokalemic form (5 familiar, 5 sporadic, 5 thyrotoxic and 1 secondary). No patient with the normokalemic form was detected. Predominance of men was found (14 patients), especially in the cases with hyperthyroidism (5 patients). No thyrotoxic patient was of oriental origin. Only 4 patients had the hyperkalemic form (3 familiar, 1 sporadic). Attacks of paralysis began during the first decade in the hyperkalemic form and up to the third decade in the hypokalemic. In both forms the attacks occurred preferentially in the morning with rest after exercise being the most important precipitating factor. Seventy five percent of the hyperkalemic patients referred brief attacks (< 12 hours). Longer attacks were referred by 43% of the hypokalemic patients. The majority of the attacks manifested with a generalized weakness mainly in legs, and its frequency was variable. Creatinokinase was evaluated in 10 patients and 8 of them had levels that varied from 1.1 to 5 times normal. Electromyography was done in 6 patients and myotonic phenomenon was the only abnormality detected in 2 patients. Carbonic anhydrase inhibitors, especially acetazolamide, were used for prophylactic treatment in 9 patients with good results in all. Although periodic paralysis may be considered a benign disease we found respiratory distress in 5 patients, permanent myopathy in 1, electrocardiographic abnormalities during crises in 4; death during paralysis occurred in 2. Therefore correct diagnosis and immediate treatment are crucial. This study shows that hyperthyroidism is an important cause of periodic paralysis in our country, even in non oriental patients. Hence endocrine investigation is mandatory since this kind of periodic paralysis will only be abated after return to the euthyroid state.

[Chronic inflammatory demyelinating polyradiculoneuropathy. Study of 18 cases]. / Polirradiculoneuropatia desmielinizante inflamatória crônica. Estudo de 18 pacientes.

This is a prospective study that describes 18 patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), idiopathic type. The patients have been followed for a period of 4 to 127 months. We evaluated the clinical characteristics, the evolution, and therapeutic response. Male patients outnumbered female patients in a proportion of 1.25:1. Symptoms first appeared at an age ranging from 6 to 85. Most of the patients denied the occurrence of preceding events and a progressive evolution prevailed over relapsing evolution. All patients had both motor and sensory dysfunction associated with loss of tendon reflexes, and only three patients (16.7%) had cranial nerve involvement. The cerebrospinal fluid protein levels were increased in 88.9% of the patients and mean level was 203.4 mg/dl. Electrophysiological studies revealed demyelination in all patients and axonal damage in 94.4%. Preponderant characteristics in the sural nerve biopsy of seven patients showed demyelination and remyelination, and changes indicative of axonal damage were often present. The anti-HLA Dr antibodies were found in the sural nerve of one patient and anti-CD3 antibodies in the sural nerve of two. All patients were first treated with prednisone. The drug was maintained in reduced doses and given in alternate days to 72.2% of the patients with success. Two patients (11.1%) are asymptomatic even after the withdrawal of all medication. We administered azathioprine, associated or not with corticoid, to the four patients who had not had a satisfactory response to the prednisone treatment. By the time of the last evaluation 16 patients (88.9%) had functional improvement.

[Magnetic resonance in HTL-I associated myelopathy. Leukoencephalopathy and spinal cord atrophy]. / Ressonância magnética na mielopatia associada ao HTLV-I. Leucoencefalopatia e atrofia medular.

Cerebral white matter lesions and spinal cord atrophy have been frequently reported in patients with HTLV-I associated myelopathy (HAM). The exact frequency and the clinical relevance of these findings still remain to be elucidated. Twenty-nine patients with HAM were studied by magnetic resonance imaging of the brain and spine. Cerebral white matter lesions equal or over 3 mm in diameter were considered abnormal. The spinal cord size was evaluated using an index we have called "spinal cord index". The radiological findings were correlated to the clinical features of the myelopathy. Cerebral white matter lesions occurred in 52% of the patients, and spinal cord atrophy in 74%. There was no significant correlation between these abnormalities and the clinical features studied. These findings suggest that the resonance imaging is a useful method for detection of cerebral and spinal cord abnormalities in HAM patients. The absence of correlation between cerebral white matter lesions and either patient age or risk factors for cardiovascular disease suggests a possible association between the leukoencephalopathy and the infection.

[Secretory meningioma. Report of two cases]. / Meningioma secretório. Relato de dois casos.

Two surgically removed meningotheliomatous meningiomas with hyaline inclusions or pseudopsammoma bodies were studied. Both meningiomas showed expression of carcinoembryonic antigen and cytokeratin in the cells surrounding the hyaline bodies. There was widespread vimentin and epithelial membrane antigen except in the cells with hyaline inclusions. Clinically both had a severe cerebral edema. One of the cases showed multiple tumors, probably meningiomas. It is important not to misinterpret this variant of meningioma as metastatic neoplasm which may result in palliative treatment of a potentially curable tumor.

Dengue. Muscle biopsy findings in 15 patients.

Dengue is known to produce a syndrome involving muscles, tendons and joints. The hallmark of this syndrome is severe myalgia but includes fever, cutaneous rash, and headache. The neuromuscular aspects of this infection are outlined only in isolated reports, and the muscle histopathological features during myalgia have not been described. In order to ascertain the actual neuromuscular involvement in dengue and better comprehend the histological nature of myalgia, we performed a clinical and neurological evaluation, a serum CPK level and a muscle biopsy (with histochemistry) in 15 patients (4 males), median age 23 years (range 14-47) with classic dengue fever, serologically confirmed, during the brazilian dengue epidemics from September 1986 to March 1987. All patients had a history of fever, headache and severe myalgia. Upon examination 4 had a cutaneous rash, 3 had fever, and 3 a small hepatomegaly. The neurological examination was unremarkable in all and included a manual muscle test. CPK was mildly elevated in only 3 patients. Muscle biopsy revealed a light to moderate perivascular mononuclear infiltrate in 12 patients and lipid accumulation in 11. Mild mitochondrial proliferation was seen in 3, few central nuclei in 3, rare foci of myonecrosis in 3, and 2 patients had type grouping. Dengue in our patients, produced myalgia but no detectable muscle weakness or other neuromuscular involvement. The main histopathological correlation with myalgia seems to be a perivascular mononuclear infiltrate and lipid accumulation.

Spinal muscular atrophy type II (intermediary) and III (Kugelberg-Welander). Evolution of 50 patients with physiotherapy and hydrotherapy in a swimming pool.

We added hydrotherapy to 50 patients with spinal muscular atrophy (SMA) who were being treated with individual conventional physiotherapy. Hydrotherapy performed at an approximate temperature of 30 degrees Celsius, twice a week, for thirty minutes in children and forty-five minutes in adults during a 2-year period. The outcome derived from this combined modality of treatment was rated according to physiotherapeutic evaluations, the MMT (Manual Muscular Test), and the Barthel Ladder. Patients were reevaluated at 2-month intervals. After two years of ongoing treatment, we were able to observe that the deformities in hip, knee and foot were progressive in all SMA Type II patients, and in some Type III. Muscle strength stabilized in most SMA Type III patients, and improved in some. MMT was not done in SMA Type II. In all patients we were able to detect an improvement in the Barthel Ladder scale. This study suggests that a measurable improvement in the quality of daily living may be obtained in patients with SMA Types II and III subjected to conventional physiotherapy when associated with hydrotherapy.

Centronuclear myopathy. Histopathological aspects in ten patients with childhood onset.

Centronuclear myopathy is a rare congenital myopathy. According to the period of onset of signs and symptoms and the degree of muscular involvement three clinical forms are distinguished: severe neonatal; childhood onset; and adult onset. We describe herein the muscle biopsy findings of ten patients with the childhood onset form of the disease including three cases with ultrastructural study. The biopsies disclosed increased nuclear centralization that varied from 25 to 90% of the fibers, type I predominance, great variability in fiber diameters, involvement in the internal fiber's architecture, and focal areas of myofilament disorganization. The main histopathologic differential diagnoses included type I fiber predominance, congenital fiber type disproportion, and myotonic dystrophy. The histologic abnormalities in centronuclear myopathy may be due to an arrest of maturation on the fetal myotubular stage. The cause of this arrest remains elusive.