Osvaldo J. M. Nascimento

Criteria for diagnosis of pure neural leprosy

Abstract.The clinical diagnosis of pure neural leprosy (PNL) remains a public health care problem mainly because skin lesions—the cardinal features of leprosy—are always absent.Moreover, the identification of the leprosy bacillus is not easily achieved even when a nerve biopsy can be performed. In an attempt to reach a reliable PNL diagnosis in patients referred to our Leprosy Outpatient Clinic, this study employed a variety of criteria. The nerve biopsies performed on the 67 individuals whose clinical, neurological, and electrophysiological examination findings strongly suggested peripheral neuropathy were submitted to M. leprae identification via a polymerase chain reaction (PCR). Mononeuropathy multiplex was the most frequent clinical and electrophysiological pattern of nerve dysfunction, while sensory impairment occurred in 89% of all cases and motor dysfunction in 81%. Axonal neuropathy was the predominant electrophysiological finding, while the histopathological nerve study showed epithelioid granuloma in 14% of the patients, acid fast bacilli in 16%, and nonspecific inflammatory infiltrate and/or fibrosis in 39%. PCR for M. leprae was positive in 47% of the nerve biopsy samples (n=23). PCR, in conjunction with clinical and neurological examination results, can be a powerful tool in attempting to identify and confirm a PNL diagnosis.

Value of nerve biopsy in the diagnosis and follow-up of leprosy: the role of vascular lesions and usefulness of nerve studies in the detection of persistent bacilli.

Abstract Nerve biopsy specimens from 53 patients with leprosy and neuropathy were taken from the sural, the dorsal branch of the ulnar, or the superficial radial nerves and processed for light and electron microscopy. There was inflammation in 40 cases (75%), 7 with a granulomatous reaction, various stages of fibrosis in 35 (66%), and endoneurial vascular neoformation in 7. In two cases, small focal infarcts were associated with marked endoneurial inflammation compressing the vessels, in addition to endoneurial lymphocytic vasculitis. Most had an axonal neuropathy of varying degree, some with total fibre loss, others with predominant small myelinated and unmyelinated fibre loss. Signs of demyelination and remyelination were the main findings in 9 cases (17%). Bacilli were present in endothelial, perineurial, Schwann cells and in macrophages. On two occasions, they lost their alcohol acid resistance, were suspected in semithin sections, and confirmed ultrastructurally. The biopsy was decisive for the diagnosis of leprosy in 15 cases (28%), most without skin lesions. We evaluated the effectiveness of the treatment in 20 (37.7%), 12 without and 8 with bacilli, despite negativity in the skin. The diagnosis of leprosy based on skin lesions was confirmed with the nerve biopsy in 9 cases, 6 had an inflammatory neuropathy suggestive of leprosy in the absence of bacilli, and 3 had nonspecific changes in the sural nerve since the neuropathy was in the upper limbs. We conclude that nerve biopsy is indicated for the diagnosis of leprosy in cases without clinically visible skin lesions and to evaluate the effectiveness of the treatment. In these cases the ultrastructural studies are important for recognition of the bacilli. Vascular lesions may play an important role in the progression of the nerve damage, including the occurrence of focal nerve infarcts which, to our knowledge, have not been previously reported in association with leprosy.

Peripheral neuropathy in HTLV-I infected individuals without tropical spastic paraparesis/HTLV-I-associated myelopathy.

Tropical spastic paraparesis/ HTLV-I-associated myelopathy (TSP/HAM) is the classical neurological manifestation of HTLV-I. Only a few studies have described isolated peripheral neuropathy (PN) among HTLV-I infected individuals. 335 infected individuals without TSP/HAM were evaluated for the presence of PN and 45 of them showed evidences of peripheral nervous system involvement. Of these 21 patients had isolated PN, defined by clinical and/or electrophysiological criteria. Sural nerve biopsies revealed inflammatory infiltrates in 2, axonal degeneration in 2 and segmental demyelination in 1. Therefore, peripheral neuropathy can be found as an isolated manifestation of HTLV-I infection. We conclude that HTLV-I infection should be investigated in patients with PN of unknown origin.

17p duplicated Charcot-Marie-Tooth 1A: characteristics of a new population.

AbstractThe most frequent type of Charcot–Marie–Tooth (CMT) neuropathy is that associated with the 17p11.2–p12 chromosome duplication, whose characteristics have been well described in European and North American populations. In this study, we analyzed a Brazilian population exhibiting the mutation, found in 57 patients from 42 families (79%) of a cohort of 53 families with demyelinating CMT. Almost 20% of the duplicated cases were sporadic. In 77% of the duplicated families the mutation event occurred in the hot spot area of the CMT1A–Rep region. Forty–five percent of patients were females, 84% were Caucasians and 13% of African descent. Distal limb weakness was the most frequent abnormality, appearing in 84% of patients, although uncommon manifestations such as severe proximal weakness, floppy baby syndrome, diaphragmatic weakness and severe scoliosis were also observed. One patient was wheelchair–bound, and three suffered severe hand weakness. Sensory abnormalities were detected in 84% of the cases, but 80% were unaware of this impairment. Twelve patients complained of positive sensory manifestations such as pain and paresthesias. Progression was reported by 40%. Motor conduction velocities in the upper limbs were always less than 35 m/s, and less than 30.4 m/s in the peroneal nerve. The findings of this study expand the clinical spectrum of the disease.

Neurologic Complications Associated With the Zika Virus in Brazilian Adults

Importance There are no prospective cohort studies assessing the incidence and spectrum of neurologic manifestations secondary to Zika virus (ZIKV) infection in adults. Objective To evaluate the rates of acute ZIKV infection among patients hospitalized with Guillain-Barré syndrome (GBS), meningoencephalitis, or transverse myelitis. Design, Setting, and Participants A prospective, observational cohort study was conducted at a tertiary referral center for neurological diseases in Rio de Janeiro, Brazil, between December 5, 2015, and May 10, 2016, among consecutive hospitalized adults (>18 years of age) with new-onset acute parainfectious or neuroinflammatory disease. All participants were tested for a series of arbovirosis. Three-month functional outcome was assessed. Interventions Samples of serum and cerebrospinal fluid were tested for ZIKV using real-time reverse-transcriptase–polymerase chain reaction and an IgM antibody-capture enzyme-linked immunosorbent assay. Clinical, radiographic (magnetic resonance imaging), electrophysiological, and 3-month functional outcome data were collected. Main Outcomes and Measures The detection of neurologic complications secondary to ZIKV infection. Results Forty patients (15 women and 25 men; median age, 44 years [range, 22-72 years]) were enrolled, including 29 patients (73%) with GBS (90% Brighton level 1 certainty), 7 (18%) with encephalitis, 3 (8%) with transverse myelitis, and 1 (3%) with newly diagnosed chronic inflammatory demyelinating polyneuropathy. Of these, 35 patients (88%) had molecular and/or serologic evidence of recent ZIKV infection in the serum and/or cerebrospinal fluid. Of the patients positive for ZIKV infection, 27 had GBS (18 demyelinating, 8 axonal, and 1 Miller Fisher syndrome), 5 had encephalitis (3 with concomitant acute neuromuscular disease), 2 had transverse myelitis, and 1 had chronic inflammatory demyelinating polyneuropathy. Admission to the intensive care unit was required for 9 patients positive for ZIKV infection (26%), and 5 (14%) required mechanical ventilation. Compared with admission during the period from December 5, 2013, to May 10, 2014 (before the Brazilian outbreak of ZIKV), admissions for GBS increased from a mean of 1.0 per month to 5.6 per month, admissions for encephalitis increased from 0.4 per month to 1.4 per month, and admissions for transverse myelitis remained constant at 0.6 per month. At 3 months, 2 patients positive for ZIKV infection (6%) died (1 with GBS and 1 with encephalitis), 18 (51%) had chronic pain, and the median modified Rankin score among survivors was 2 (range, 0-5). Conclusions and Relevance In this single-center Brazilian cohort, ZIKV infection was associated with an increase in the incidence of a diverse spectrum of serious neurologic syndromes. The data also suggest that serologic and molecular testing using blood and cerebrospinal fluid samples can serve as a less expensive, alternative diagnostic strategy in developing countries, where plaque reduction neutralization testing is impractical.

Leprosy neuropathy: clinical presentations

Leprosy is a chronic infectious peripheral neuropathy caused by Mycobacterium leprae. The different clinical presentations of the disease are determined by the quality of the host immune response. Early detection of leprosy and treatment by multidrug therapy are the most important steps in preventing deformity and disability. Thus the early recognition of the clinical leprosy presentation is essential. Mononeuritis, mononeuritis multiplex (MM), polyneuritis (MM summation) are the most frequent. The frequent anesthetic skin lesions are absent in the pure neuritic leprosy presentation form. Isolated peripheral nerve involvement is common, including the cranial ones. Arthritic presentation is occasionally seen, usually misdiagnosed as rheumatoid arthritis. Attention should be given to autonomic dysfunctions in leprosy. There are clinical presentations with severe neuropathic pain - painful small-fiber neuropathy. Leprous late-onset neuropathy (LLON) clinical presentation should be considered facing a patient who develop an inflammatory neuropathy many years after a previous skin leprosy treatment.

Neurological manifestations in HTLV-I-infected blood donors

The human T-cell lymphotropic virus type 1 (HTLV-I) causes a neurological disease known as HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in a minority of infected individuals. Although other neurological outcomes have been described their prevalence is presently unknown. To evaluate the frequency and characteristics of neurological involvement in a population of HTLV-I-infected blood donors we investigated 196 HTLV-I positive and 196 negative blood donors from a blood center of Rio de Janeiro, Brazil. Individuals with abnormalities at the neurological examination were examined by three neurologists, and when pertinent, additional neurological investigations were performed. Descriptive analysis, Students t-test and chi2 test were employed for statistical analysis. Neurological abnormalities were found in 71 (36.2%) of the HTLV-I positive blood donors and in only 29 (14.8%) of the HTLV-I negative donors (OR = 2.54, 95% CI = 1.67-3.59, p = 0.000002). Cases of myelopathy, motor neuron disease and myopathy were only found in the HTLV-I positive group. In addition, peripheral neuropathy (PN) was significantly more frequent in the positive group (p = 0.015). In summary, our data suggest that HTLV-I-infected individuals exhibit a wide variety of neurological manifestations apart from the classical picture of HAM/TSP.

Amyotrophic lateral sclerosis: new perpectives and update

Amyotrophic lateral sclerosis (ALS), Charcot’s disease or Lou Gehrig’s disease, is a term used to cover the spetrum of syndromes caracterized by progressive degeneration of motor neurons, a paralytic disorder caused by motor neuron degeneration. Currently, there are approximately 25,000 patients with ALS in the USA, with an average age of onset of 55 years. The incidence and prevalence of ALS are 1-2 and 4-6 per 100,000 each year, respectively, with a lifetime ALS risk of 1/600 to 1/1000. It causes progressive and cumulative physical disabilities, and leads to eventual death due to respiratory muscle failure. ALS is diverse in its presentation, course, and progression. We do not yet fully understand the causes of the disease, nor the mechanisms for its progression; thus, we lack effective means for treating this disease. In this chapter, we will discuss the diagnosis, treatment, and how to cope with impaired function and end of life based on of our experience, guidelines, and clinical trials. Nowadays ALS seems to be a more complex disease than it did two decades – or even one decade – ago, but new insights have been plentiful. Clinical trials should be seen more as experiments on pathogenic mechanisms. A medication or combination of medications that targets more than one pathogenic pathway may slow disease progression in an additive or synergistic fashion.

Normative data for Aδ contact heat evoked potentials in adult population: a multicenter study.

Abstract There has been a significant increase over recent years in the use of contact heat evoked potentials (CHEPs) for the evaluation of small nerve fiber function. Measuring CHEP amplitude and latency has clinical utility for the diagnosis and assessment of conditions with neuropathic pain. This international multicenter study aimed to provide reference values for CHEPs to stimuli at 5 commonly examined body sites. Contact heat evoked potentials were recorded from 226 subjects (114 females), distributed per age decade between 20 and 79 years. Temperature stimuli were delivered by a thermode (32°C-51°C at a rate of 70°C/s). In phase I of the study, we investigated side-to-side differences and reported the maximum normal side-to-side difference in A&dgr; CHEP peak latency and amplitude for leg, forearm, and face. In phase II, we obtained normative data for 3 CHEP parameters (N2P2 amplitude, N2 latency, and P2 latency), stratified for gender and age decades from face, upper and lower limbs, and overlying cervical and lumbar spine. In general, larger CHEP amplitudes were associated with higher evoked pain scores. Females had CHEPs of larger amplitude and shorter latency than males. This substantive data set of normative values will facilitate the clinical use of CHEPs as a rapid, noninvasive, and objective technique for the assessment of patients presenting with neuropathic pain.

Guidelines to diagnosis and monitoring of Fabry disease and review of treatment experiences.

Ana Maria Martins, MD, PhD, Vânia D’Almeida, MD, Sandra Obikawa Kyosen, MD, Edna Tiemi Takata, MD, Alvimar Goncalves Delgado, MD, PhD, Ângela Maria Barbosa Ferreira Goncalves, MD, Caio Cesar Benetti Filho, MD, Dino Martini Filho, MD, Gilson Biagini, MD, Helena Pimentel, MD, Hugo Abensur, MD, PhD, Humberto Cenci Guimaraes, MD, Jaelson Guilhem Gomes, MD, Jose Sobral Neto, MD, PhD, Luiz Octavio Dias D’Almeida, PhD, Luiz Roberto Carvalho, MD, Maria Beatriz Harouche, MD, Maria Cristina Jacometti Maldonado, MD, Osvaldo J. M. Nascimento, PhD, Paulo Sergio dos Santos Montoril, MD, and Ricardo Villela Bastos, MD