Luiz Felipe Rocha Vasconcellos

Organophosphate-induced delayed neuropathy: case report

A neuropatia tardia dos organofosforados (NTOF) e condicao clinica incomum. Geralmente ocorre apos a intoxicacao aguda por organofosforados, seguindo-se a fase de hiperestimulacao colinergica. O quadro clinico e caracterizado por deficit motor distal nos membros inferiores associado a sintomas sensitivos. O estudo eletroneuromiografico tem demonstrado padrao axonal motor na maioria dos casos. Podem ocorrer sinais de comprometimento do sistema nervoso central. Descrevemos o caso de uma paciente de 39 anos que ingeriu inseticida a base de Dichlorvos e quatorze dias apos apresentou quadro de hiperestesia associado a paresia distal nos membros inferiores. Realizou eletroneuromiografia que se caracterizou por padrao compativel com polineuropatia axonal. Sinais piramidais, de aparecimento mais tardio, foram observados nos membros superiores. Diante do comprometimento do sistema nervoso periferico e central, tambem consideramos o termo neuropatia tardia por organofosforado (NTOF) mais adequado do que tao somente polineuropatia tardia por organofosforado (PTOF).Organophosphate induced delayed neuropathy (OPIDN) is an uncommon clinical condition. It occurs in association with the ingestion of great amounts of organophosphate after the stimulation of cholinergic receptor. The clinical picture is characterized by a distal paresis in lower limbs associated with sensitive symptoms. Electrodiagnostic studies show a motor axonal neuropathy. Involvement of the central nervous system may occur. We describe a 39 years-old female patient who developed hyperesthesia associated with lower limbs paresis, fourteen days after she had ingested a Dichlorvos-based insecticide. Electrophysiological study was characterized by an axonal polyneuropathy pattern. Pyramidal tract dysfunction was observed later in upper limbs. Considering that both peripheral and central nervous systems are involved we believe that the more appropriated term would be organophosphate induced delayed neuropathy (OPIDN) instead of organophosphate induced delayed polyneuropathy (OPIDP).

Hoffman's syndrome: pseudohypertrophic myopathy as initial manifestation of hypothyroidism. Case report

The frequency of myopathy in hypothyroidism ranges from 30 to 80%. The major symptoms related are weakness, muscular cramps and myalgia. The pseudohyperthrophic form is called Hoffmans syndrome. The electrophysiological study reveals myopathy, neuropathy or mixed pattern. Laboratorial investigation generally shows increased levels of muscle enzymes and low serum thyroid hormones, with thyrotrophic-stimulating hormone (TSH) elevated. The treatment consists in hormone replacement and the prognosis is good in most of the cases. We report an adult male who developed muscular cramps, myalgia, weakness, pseudohyperthrophy, associated with facial edema and alteration of his voice. The muscle enzymes were increased and T4 was undetectable with a raised level of TSH. The myopathy was the initial manifestation of hypothyroidism in this case.

Frontal functions in depressed and nondepressed Parkinson's disease patients: Impact of severity stages

Severity of Parkinsons disease (PD) and frontal impairment are positively correlated. Testing frontal functions in depressed/nondepressed PD patients with different severity stages may reveal whether depression leads to this impairment. We aimed to relate severity of PD to frontal functional impairment and to test if negative stimuli/depressive symptoms interfered with frontal tasks. The Stroop test and the Emotional Stroop test were performed by 46 PD patients, 18 of whom were depressed. The Hoehn and Yahr scale assessed severity of the disease. We calculated the difference in seconds for each Stroop card and the interference index (C/D) between depressed and nondepressed patients sharing the same severity of disease. The differences among the groups (depressed and nondepressed) according to the severity of the disease (mild and moderate) were compared using the Mann-Whitney test. The depressed patients had a poorer performance on the test than the nondepressed PD patients, although the difference was not statistically significant. In conclusion, there is a clinically relevant but not statistically significant difference on the performance of frontal tasks between depressed and nondepressed PD patients. Neither depression nor the severity of the disease were determinant to the poorer performance on the Stroop and the Emotional Stroop tests.

Parkinson's disease dementia: Diagnostic criteria and risk factor review.

Cognitive impairment in Parkinson’s disease (PD) greatly affects the morbidity and mortality rates of the disease and can be present as mild executive dysfunction even in the early stages. In advanced PD, the prevalence of dementia (PDD) reaches more than 80%. The Movement Disorders Society (MDS) has proposed diagnostic criteria for PDD and Mild Cognitive Impairment (MCI) in PD, raising the sensibility and specificity of those diagnoses compared with DSM IV, for example. Cognition impairment is an important issue to determine in PD because of therapeutic, epidemiologic, and prognostic factors. These guidelines should be applied to a diagnosis of PD-MCI and PDD as soon as possible in order to provide a correct diagnosis. Another important topic to discuss regarding cognition in PD is which patient would be more likely to develop PDD. There are some risk factors for cognitive impairment in PD with cumulative risk. Important risk factors related to PDD are age, time of diagnosis, rigid-akinetic phenotype, severe impairment, impairment of semantic fluency, genetic factors, low education level, and postural instability. Recognizing them is also important for early diagnosis. We discuss the diagnostic criteria of PD cognitive impairment and some aspects of risk factors related to it in this review.

Neuroimaging in Parkinsonism: a study with magnetic resonance and spectroscopy as tools in the differential diagnosis

The differential diagnosis of Parkinsonism based on clinical features, sometimes may be difficult. Diagnostic tests in these cases might be useful, especially magnetic resonance imaging, a noninvasive exam, not as expensive as positron emission tomography, and provides a good basis for anatomical analysis. The magnetic resonance spectroscopy analyzes cerebral metabolism, yielding inconsistent results in parkinsonian disorders. We selected 40 individuals for magnetic resonance imaging and spectroscopy analysis, 12 with Parkinsons disease, 11 with progressive supranuclear palsy, 7 with multiple system atrophy (parkinsonian type), and 10 individuals without any psychiatric or neurological disorders (controls). Clinical scales included Hoenh and Yahr, unified Parkinsons disease rating scale and mini mental status examination. The results showed that patients with Parkinsons disease and controls presented the same aspects on neuroimaging, with few or absence of abnormalities, and supranuclear progressive palsy and multiple system atrophy showed abnormalities, some of which statistically significant. Thus, magnetic resonance imaging and spectroscopy could be useful as a tool in differential diagnosis of Parkinsonism.

Síndrome psicótica evoluindo com demência como manifestação clinica de deleção do DNA mitocondrial

The manifestations of mitochondrial disease are variable, affecting more frequently the organs with high aerobic metabolism in which they are more abundant, for example the nervous system. The beginning of symptoms in general is observed at chilhood, but some patients presented on adult age. We present an atypical case associated with mitochondrial DNA deletion. A 39-years-old man with psychiatric symptoms that configured initial clinical picture and only after 12 years of the beginning of symptoms neurological alterations became noticeable. The diagnosis of mitochondrial illness was confirmed by muscle biopsy being documented mitochondrial DNA deletion.

Mielopatia por deficiência de vitamina B12 apresentando-se como mielite transversa

Vitamin B12 deficiency may induce neuropathy, myelopathy, dementia and optic neuropathy. The diagnosis is established by vitamin B12, homocysteine and methylmalonic acid measurements. Myelin and axon destruction in the white matter of the spinal cord are observed. The posterior column of the cervical and thoracic level is the most common involved area. The involvement of the anterior column is restricted to advanced and relatively severe cases. Treatment is based on vitamin B12 injections, and the prognosis depends on the stage of vitamin deficiency and deterioration at treatment onset. We report a case with transverse myelitis due to vitamin B12 deficiency. This picture is relatively uncommon, however, we believe patients with transverse myelitis should have vitamin B12 studies as part of the diagnosis work up.

Isolated Central Nervous System Vasculitis as a Manifestation of Neurosarcoidosis.

A 62-year-old male presented to our clinic with recurrent fever, skin lesions (petechiae), scleral wounds, and hilar adenomegaly. A diagnosis of sarcoidosis was established, which resolved with corticosteroid treatment. After a few months, the patient developed confusion and behavioral changes, with few objective neurological deficits. Brain magnetic resonance imaging showed slight focal meningeal enhancement (prepontine region). The level of angiotensin-converting enzymes was normal in the serum and increased in the cerebrospinal fluid. The patient was diagnosed with neurosarcoidosis, and corticosteroid treatment was prescribed, yielding good clinical response. Nine months later, the patient presented with multiple ischemic strokes, and arteriography demonstrated multiple distal irregularities in all arterial territories, suggesting cerebral vasculitis. Even with corticosteroids, cyclophosphamide, and intravenous immunoglobulin, the patient died. Vasculitis is rarely seen in association with sarcoidosis, and in this case, no systemic manifestation was observed at the time that the patient developed vasculitis.

Clinical profiles associated with LRRK2 and GBA mutations in Brazilians with Parkinson's disease.

BACKGROUND Parkinsons disease (PD) is a neurodegenerative disorder characterized by remarkable phenotypic variability. Accumulated evidence points that the manifestation of PD clinical signs might be differentially modified by genetic factors, as mutations in LRRK2 and GBA genes. In this sense, the clarification of the genotype-phenotype correlations in PD has important implications in predicting prognosis and can contribute to the development of specific therapeutic approaches. METHODS Here, we conducted the first comparative analysis of motor and non-motor features in 17 LRRK2 and 22 GBA mutation carriers and 93 non-carriers unrelated PD patients from Brazil, a highly admixed population. RESULTS Significant differences were found between the three groups. LRRK2 PD patients presented more occurrence of familiar history. Resting tremor was observed in a lower frequency in GBA mutation carries. In contrast, gait freezing and dysautonomia was present in lower frequencies in LRRK2 carriers. Besides that, LRRK2 and GBA mutation carriers showed a higher incidence of depressive symptoms and a younger age at onset, when compared to non-carriers. CONCLUSION Our results suggest that specific mutations in GBA and LRRK2 influence the clinical signs of the disease, with significant implications for handling of specific patient groups.

Autosomal dominant Parkinson's disease: Incidence of mutations in LRRK2, SNCA, VPS35 and GBA genes in Brazil.

INTRODUCTION Amongst Parkinsons disease (PD) genetic factors, mutations in LRRK2, SNCA, VPS35 and GBA genes are recognized causes of PD. Nonetheless, few genetic screenings have been conducted in families with a history of PD consistent with autosomal dominant inheritance (ADPD), and their relevance to the etiology of PD has been poorly explored in Latin American populations, such as the Brazilian one, with a high degree of admixture. METHODS In order to assess the contribution of specific mutations in LRRK2, SNCA, VPS35 and GBA genes to ADPD in Brazil, we conducted the first molecular evaluation in a cohort of 141 index cases from families with ADPD. Genomic DNA was isolated from peripheral blood or saliva, and the molecular analysis was performed by TaqMan allelic discrimination assays or bidirectional sequencing. RESULTS Heterozygous mutations in LRRK2 and GBA genes were identified in 10 (7.0%) probands, and all presented typical signs of classical PD. No mutations were found in SNCA or VPS35 genes. CONCLUSION Our findings in a representative series of index cases from families with ADPD emphasize the important contribution of LRRK2 G2019S and GBA (L444P and N370S) mutations to parkinsonism in Brazilian families. The absence of mutations in VPS35 and SNCA genes reveals that they are uncommon causes of PD in Brazil, corroborating previous studies that also failed to detect these genetic variants in PD patients from other populations. Recent discoveries of novel causative genes of autosomal dominant forms of PD expand the investigative possibilities and should be targeted on future studies.