OBJECTIVE: To analyze a series of patients with neuromyotonia from neuromuscular disorders unit, ... more OBJECTIVE: To analyze a series of patients with neuromyotonia from neuromuscular disorders unit, Hospital de Clinicas da Universidade Federal do Parana. BACKGROUND: Neuromyotonia is a rare disease characterized by spontaneous and continuous muscle activity due to a disorder of the peripheral nerve hyperexcitability. Patients develop persistent muscle contraction, classically worsening after exercise. Electromyography is characterized by neuromyotonic discharges and about 40% of patients have detectable voltage-gated potassium-channel (VGKC) antibodies. DESIGN/METHODS: We studied four patients with neuromyotonia, regarding the clinical, electrophysiological and immunological findings. RESULTS: The average age of onset of symptoms was 17.5 (7-35) years and there was no gender predilection. The average time between onset of symptoms and diagnosis was 9.5 (1-29) years. The patients had muscle twitching (100%), muscle hypertrophy and hyperhidrosis (100%), muscle cramps and stiffness (75%), pseudomyotonia (25%), weakness (75%), paresthesias (25%), dysphonia, dysphagia and dyspnea (25%) and central nervous system symptoms (25%). Family history and exogenous intoxication were negative. All patients had the dosage of anti-VGKC negative. Electrophysiological findings: myokymia and neuromyotonic discharges were found in all patients, douplets and multiplets in 100% and triplets in 50% of cases. The maximum intraburst frequency ranged from 70 to 200 Hz. Three patients were treated with carbamazepine and gabapentin with a good response to treatment. Three used phenytoin, and of these, two had a partial response and one had intolerance to the drug. One patient had epilepsy, one patient developed ulcerative colitis idiopathic, glomerulonephritis and eczema on the face and another one hypothyroidism, arthralgia and myalgia. CONCLUSIONS: The diagnosis of neuromyotonia is accomplished primarily through clinical and electrophysiological findings. Electromyography often confirms diagnosis by the presence of neuromyotonic discharges. The dosage of anti-CKVD has a low sensitivity for the diagnosis of disease. The association with autoimmune diseases can be observed, as described in this series. Disclosure: Dr. Scola has received personal compensation for activities with Merck Serono as scientific advisor board. Dr. Paranhos has nothing to disclose. Dr. Lorenzoni has nothing to disclose. Dr. Kay has nothing to disclose. Dr. Vincent has received personal compensation for activities with Athena Diagnostics. Dr. Vincent has received royalty payments from Athena Diagnostics. Dr. Werneck has nothing to disclose.
Background: The most prevalent autoimmune diseases (AID) of the Central Nervous System (CNS) are ... more Background: The most prevalent autoimmune diseases (AID) of the Central Nervous System (CNS) are Multiple Sclerosis (MS) and Neuromyelitis Optica Spectrum Disorder (NMOSD), both being demyelinating diseases. Recent studies show that patients with CNS demyelinating diseases have a higher risk of presenting associated diagnosis of another AIDs. Objectives: The present study aimed to evaluate the frequency of autoimmune comorbidities and autoantibodies in patients with MS and NMOSD. Design and setting: Were analyzed the medical records of 126 patients with MS or NMOSD, from the Demyelinating Diseases Outpatient Clinic in the Neurological and Psychiatric Unit in the Complexo Hospital de Clinicas da Universidade Federal do Parana (CHC-UFPR), taking in consideration the presence of AIDs and autoantibodies. Methods: The variables were organized in a Microsoft® Office Excel spreadsheet for statistical analysis. Results: Of the 126 analyzed cases, 111 (88%) corresponded to MS and 15 (12%) to NMOSD. From the total, at least one AID was associated in 11 patients (8.7%), six of which were diagnosed with MS and five with NMOSD (p<0.05). Regarding autoantibodies, there were 21 cases (16.7%) in which antinuclear antibodies (ANA) were present, and 12 cases (9.5%) in which autoantibodies other than ANA were present (p<0.05). Conclusions: The results of the study showed a higher frequency of AIDs in patients with CNS demyelinating diseases compared to the normal population. The results found in this study may contribute to improve the treatment and follow-up of patients with CNS demyelinating diseases, so that the concomitance of other AIDs is considered by the clinician.
Necrotizing myopathy (NM) can occur with drug abuse, use of toxic agents, autoimmune diseases, an... more Necrotizing myopathy (NM) can occur with drug abuse, use of toxic agents, autoimmune diseases, and neoplasia. The aim of this report is to demonstrate that NM can be the first manifestation of human immunodeficiency virus (HIV) infection. A 20-year-old man presented with progressive proximal weakness and diffuse myalgias for 1 month, associated with fever and lymphadenopathy for most of this time. He denied use of statins or illicit drugs. He had a temperature of 37.88C, lymphadenopathy, diffuse edema, bilateral peripheral facial palsy, nasal voice, impaired palate elevation, limb hypotonia, and proximal weakness in the upper and lower limbs [Medical Research Council (MRC) grade 3]. Laboratory tests on admission showed creatine kinase of 26,167 U/L (normal 30–200 U/L), C-reactive protein of 2.76 mg/dl (normal <0.5 mg/dl), positive HIV serology, CD4 count of 300 cells/mm, CD4/CD8 ratio of 0.7, and viral load of 50,027 copies. Anti-nuclear antibody titers and serological tests for hepatitis, cytomegalovirus, toxoplasmosis, syphilis, and Epstein–Barr virus were negative. Nerve conduction studies were normal. Needle electromyography revealed fibrillation potentials and polyphasic motor unit potentials of short duration and low amplitude in the brachial biceps muscle. MRI showed hyperintensity in short-tau inversion recovery (STIR)–weighted images and mild contrast enhancement in the brachial biceps and vastus lateralis muscles. Muscle biopsy was suggestive of NM (Fig. 1). Therapy was initiated with antiretroviral drugs and prednisone 60 mg/day. After 1 month of therapy, weakness worsened (MRC grade 2), and CK levels remained elevated (17,220 U/L). Intravenous immunoglobulin (400 mg/kg/day for 5 days) was administered, which resulted in marked and progressive improvement of weakness. Evaluation 1 month later revealed a CK of 139 U/L, CD4 count of 1,179 cells/mm, CD4/CD8 ratio 1.66, and an undetectable viral load. After 2 years of treatment, the patient was asymptomatic on antiretroviral therapy. Myalgias and weakness are common symptoms in HIV patients during all stages of disease and may be due to viremia, antiretroviral therapy, or myopathy associated with the virus. Histological studies have demonstrated that muscle involvement in HIV is more common than previously suspected. Reports of NM associated with HIV are rare, and have occurred in chronic HIV patients, some of whom were treated with antiretroviral drugs. Our patient had NM as the initial manifestation of HIV infection. NM should be differentiated from other myopathies related to HIV, because it is potentially reversible with treatment. The definitive test for diagnosis of NM is muscle biopsy, which shows necrotic and regenerating muscle fibers with no or mild inflammation. Membrane attack complex deposition may also be present in small vessels and/or muscle fibers, and major histocompatibility complex class 1 (MHC 1) may be upregulated. The patient showed improvement after treatment with intravenous immunoglobulin. There is little information about the importance of antiretroviral therapy in patients with NM and HIV, but in this patient the antiretroviral treatment did not lead to rapid improvement in the myopathy. Although this patient did improve, the prognosis of NM associated with HIV remains unknown.
Treatment of multiple sclerosis (MS) has progressed significantly in recent years and now include... more Treatment of multiple sclerosis (MS) has progressed significantly in recent years and now includes immunosuppressants, immunomodulators, biologics and, more recently, medications that interfere with the release or maturation of lymphocytes. These medications have been shown to reduce the number of relapses, but the results in terms of reduced disability have been modest as most of the studies carried out were generally restricted to two years 1,2. Since the introduction of immunomodulators to treat MS, the response has been found to vary from patient to patient and with the research center where the study was conducted 3. To find a factor that influences the evolution of MS in patients treated with disease modifying therapies (DMTs), several
Greenfield, em 1933, relatou os casos de duas crianças que evoluíram normalmente até o segundo an... more Greenfield, em 1933, relatou os casos de duas crianças que evoluíram normalmente até o segundo ano de vida e que, progressivamente, perderam a capacidade para deambular, acompanhada de déficit intelectual, arreflexia, hipotonia muscular, sinais de envolvimento de tratos longos com atitudes de descerebração no final da vida, cuja característica patológica era o desaparecimento da oligodendroglia interfascicular •™. Em 1938, Einarson e Neel notaram que esta forma de esclerose cerebral se corava metaci omaticamente com corantes básicos da anilina e, em 1942, utilizaram pela primeira vez o termo leucoencefalopatia metacromática 11. Em 1950, Brain e Greenfield sugeriram que a metacromasia da leucoencefalopatia metacromática era devida ao acúmulo de ésteres do ácido sulfürico 20 , mas foi somente Jatskewitz, em 1958, que demonstrou serem na verdade sulfatídeos 42. Austin, em 1957, revelava que estas substâncias também estavam presentes em outros órgãos fora do sistema nervoso, como, por exemplo, o rim 3 » 4. Em 1963, Austin e col. 7 « !, » 10 e Mehl e Jatskewitz 40 , demonstraram que na leucodistrofia metacromática existia deficiência de arilsulfatase A, uma enzima que regula o metabolismo dos sulfatídeos, transformando-os em cerebrosídeos, o que seria a causa da doença. Tivemos a oportunidade de estudar dois pacientes que apresentavam leucodistrofia metacromática. Pela raridade de casos descritos no Brasil e para difundir os métodos empregados no diagnóstico, julgamos válido este relato. OBSERVAÇÕES Caso 1-IFB, sexo feminino, cor branca, 2 anos e 10 meses. Nascida de gestação e parto normais, controlou a cabeça aos três meses, sentou aos cinco meses e engatinhou aos oito meses. Andou com dezoito meses e falou com 24 meses. Nfto chegou a controlar os esfintercs. Logo após iniciar a marcha sem auxilio passou a ter dificuldade
RESUMO-Os autores relatam um caso de plexopatia lombossacra em criança e em que a extensa investi... more RESUMO-Os autores relatam um caso de plexopatia lombossacra em criança e em que a extensa investigação, incluindo ressonância nuclear magnética normal, biópsia muscular compatível com desinervação inicial e eletromiografia normal, afastou condições associadas. O paciente apresentava dor intensa, fraqueza e atrofia do membro inferior esquerdo, reflexo aquileu ausente e reflexo patelar diminuído à esquerda. Parestesia no membro envolvido acompanhava o quadro. O tratamento realizado foi dexametasona por um mês e morfina intratecal durante três meses. A evolução foi favorável, apresentando, após um ano, atrofia discreta do membro acometido e leve paresia do músculo iliopsoas esquerdo. PALAVRAS-CHAVE: plexo lombossacro, neuropatía, idiopatia. Idiopathic lumbosacral plexus neuropathy in childhood: case report ABSTRACT-We describe a lumbosacral plexus neuropathy case in childhood in which detailed investigation, including eletromyography and magnetic resonance imaging, was normal. Muscle biopsy showed mild denervation. No underlyng condition was detected. The patient presented with pain, weakness and light atrophy in left lower limb, reduced reflex at the ankle, loss of the quadriceps reflex and paresthesy in involved limb. Recovery after one year was almost complete, with persistent slight weakness and atrophy.
OBJECTIVE: To analyze a series of patients with neuromyotonia from neuromuscular disorders unit, ... more OBJECTIVE: To analyze a series of patients with neuromyotonia from neuromuscular disorders unit, Hospital de Clinicas da Universidade Federal do Parana. BACKGROUND: Neuromyotonia is a rare disease characterized by spontaneous and continuous muscle activity due to a disorder of the peripheral nerve hyperexcitability. Patients develop persistent muscle contraction, classically worsening after exercise. Electromyography is characterized by neuromyotonic discharges and about 40% of patients have detectable voltage-gated potassium-channel (VGKC) antibodies. DESIGN/METHODS: We studied four patients with neuromyotonia, regarding the clinical, electrophysiological and immunological findings. RESULTS: The average age of onset of symptoms was 17.5 (7-35) years and there was no gender predilection. The average time between onset of symptoms and diagnosis was 9.5 (1-29) years. The patients had muscle twitching (100%), muscle hypertrophy and hyperhidrosis (100%), muscle cramps and stiffness (75%), pseudomyotonia (25%), weakness (75%), paresthesias (25%), dysphonia, dysphagia and dyspnea (25%) and central nervous system symptoms (25%). Family history and exogenous intoxication were negative. All patients had the dosage of anti-VGKC negative. Electrophysiological findings: myokymia and neuromyotonic discharges were found in all patients, douplets and multiplets in 100% and triplets in 50% of cases. The maximum intraburst frequency ranged from 70 to 200 Hz. Three patients were treated with carbamazepine and gabapentin with a good response to treatment. Three used phenytoin, and of these, two had a partial response and one had intolerance to the drug. One patient had epilepsy, one patient developed ulcerative colitis idiopathic, glomerulonephritis and eczema on the face and another one hypothyroidism, arthralgia and myalgia. CONCLUSIONS: The diagnosis of neuromyotonia is accomplished primarily through clinical and electrophysiological findings. Electromyography often confirms diagnosis by the presence of neuromyotonic discharges. The dosage of anti-CKVD has a low sensitivity for the diagnosis of disease. The association with autoimmune diseases can be observed, as described in this series. Disclosure: Dr. Scola has received personal compensation for activities with Merck Serono as scientific advisor board. Dr. Paranhos has nothing to disclose. Dr. Lorenzoni has nothing to disclose. Dr. Kay has nothing to disclose. Dr. Vincent has received personal compensation for activities with Athena Diagnostics. Dr. Vincent has received royalty payments from Athena Diagnostics. Dr. Werneck has nothing to disclose.
Background: Polyneuropathies are characterized by a symmetrical impairment of the peripheral nerv... more Background: Polyneuropathies are characterized by a symmetrical impairment of the peripheral nervous system, resulting in sensory, motor and/or autonomic deficits. Due to the heterogeneity of causes, an etiological diagnosis for polyneuropathy is challenging. Objective: The aim of this study was to determine the main causes of polyneuropathy confirmed by electrodiagnostic (EDX) tests in a tertiary service and its neurophysiological aspects. Methods: This observational cross-sectional study from a neuromuscular disorders center included individuals whose electrodiagnostic tests performed between 2008 and 2017 confirmed a diagnosis of polyneuropathy. Through analysis of medical records, polyneuropathies were classified according to etiology and neurophysiological aspect. Results: Of the 380 included patients, 59.5% were male, with a median age of 43 years. The main etiologies were: inflammatory (23.7%), hereditary (18.9%), idiopathic (13.7%), multifactorial (11.1%), and diabetes (10.8...
Background: The peripheral polyneuropathies have etiological heterogeneity, with more than a hund... more Background: The peripheral polyneuropathies have etiological heterogeneity, with more than a hundred known causes. In addition, they have a lack of information related to their epidemiology. Objectives: The aim of this study is to determine the prevalence of each etiology of polyneuropathy in a single specialized center from Southern Brazil and to correlate main clinical manifestations and electrophysiological aspects. Design and setting: Observational cross-sectional study. Neuromuscular disorder center from a tertiary service. Methods: This study comprised individuals with electrodiagnostic tests compatible with polyneuropathy from a neuromuscular disorder center. Selected patients were those who underwent nerve conduction studies between 2008 and 2017. Through analysis of medical records, polyneuropathies were classified according to etiology and neurophysiological aspect. Results: The sample population consisted of 380 patients who has a male predominance (59.5%), with a median ...
N euromyelitis optica (NMO) is a rare autoimmune disorder of the central nervous system that main... more N euromyelitis optica (NMO) is a rare autoimmune disorder of the central nervous system that mainly affects the optic nerves and spinal cord related with serum autoantibodies to aquaporin-4 (1). In addition, the term “astrocytopathy” has been proposed because histopathological studies have shown that astrocyte injury is the primary event, which occurs in the active lesions of NMO (2). In 1894, on the Congrès Français de Médecine in Lyon, Eugène Devic (1858–1930) presented an article in which he called the disease “neuro-myélite optique aiguë.” In the same year, Devic’s student Fernand Gault (1873–1936) published his doctoral thesis, entitled “De la neuro-myélite optique aiguë.” Gault’s work is commonly considered to be the first review of NMO, and the disease was named after Devic in 1907 (3–5). However, previously in 1870, in his famous lecture On the Ophthalmoscopic Signs of Spinal Disease (6), Thomas Clifford Allbutt (Fig. 1) briefly mentioned a patient with acute myelitis and “a sympathetic eye disorder.” This case is considered the first account of a patient with NMO in the literature. Apart from the phylogenetic discussion of the NMO, the work of Professor Allbutt allowed us to deepen the theme by engaging the importance of ophthalmological evaluation in neurology.
We reported one patient with Charcot-Marie-Tooth type 4C (CMT4C) who developed seropositive myast... more We reported one patient with Charcot-Marie-Tooth type 4C (CMT4C) who developed seropositive myasthenia gravis. Neuromuscular junction alterations in CMT4C patients have not yet been reported. However, few patients have been reported to simultaneously have MG and CMT, but none with CMT4C. Our report suggests that additional research is required to confirm whether genetic neuropathies may predispose to MG.
In 1951, the physiologist George Duncan Dawson presented his work with the averaging of the signa... more In 1951, the physiologist George Duncan Dawson presented his work with the averaging of the signal in the evoked potentials (EPs), opening a new stage in the development of clinical neurophysiology. The authors present aspects of Professor Dawson’s biography and a review of his work on the EPs and, mainly, the article reveals the new technique in detail that would allow the growth of the clinical application of the visual, auditory, and somatosensory EPs.
This paper reviews some aspects of the life and work of Professor Johann Friedrich Horner, on the... more This paper reviews some aspects of the life and work of Professor Johann Friedrich Horner, on the occasion of the 190th anniversary of his birthday and 152 years after the publication of "Über eine Form von Ptosis". It also shows the importance of the historical description of ptosis, myosis and anhidrosis associating those symptoms with sympathetic cervical damage. He pharmacologically confirmed the impairment of sympathetic innervation to the eye and preserved parasympathetic function.
Congenital myasthenic syndromes (CMS) are heterogeneous genetic diseases in which neuromuscular t... more Congenital myasthenic syndromes (CMS) are heterogeneous genetic diseases in which neuromuscular transmission is compromised. CMS resembling the Lambert-Eaton myasthenic syndrome (CMS-LEMS) are emerging as a rare group of distinct presynaptic CMS that share the same electrophysiological features. They have low compound muscular action potential amplitude that increment after brief exercise (facilitation) or high-frequency repetitive nerve stimulation. Although clinical signs similar to LEMS can be present, the main hallmark is the electrophysiological findings, which are identical to autoimmune LEMS. CMS-LEMS occurs due to deficits in acetylcholine vesicle release caused by dysfunction of different components in its pathway. To date, the genes that have been associated with CMS-LEMS are AGRN, SYT2, MUNC13-1, VAMP1, and LAMA5. Clinicians should keep in mind these newest subtypes of CMS-LEMS to achieve the correct diagnosis and therapy. We believe that CMS-LEMS must be included as an important diagnostic clue to genetic investigation in the diagnostic algorithms to CMS. We briefly review the main features of CMS-LEMS.
Children with a congenital myasthenic syndrome (CMS) who present with fatigability or weakness wi... more Children with a congenital myasthenic syndrome (CMS) who present with fatigability or weakness with symptoms confined to a limb-girdle distribution may be easily mistaken for having a congenital myopathy or muscular dystrophy. We report a patient with limb-girdle CMS (LG-CMS) due to a DOK7 mutation who presented with minicore areas in her muscle biopsy. A 10-year-old girl, born prematurely, presented with respiratory difficulty since birth. At 6 years of age she had progressive weakness that first affected the proximal muscles in the arms and legs, and changed according to physical activity. There were no delayed motor milestones or relatives with similar symptoms. On neurological examination she had mild symmetrical eyelid ptosis and facial weakness, mild proximal muscle atrophy in the arms, scapular winging, symmetrical proximal weakness in the arms [Medical Research Council (MRC) grade 3] and legs (MRC grade 4), axial muscle weakness with scoliosis and lordosis, and reduced tendon reflexes in the arms. The initial diagnosis was CMS or congenital myopathy, but serum creatine kinase levels were normal. Repetitive nerve stimulation showed >10% decrement in the musculocutaneous and spinal accessory nerves but no decrement in the facial, ulnar, or median nerves. Needle electromyography revealed low-amplitude, short-duration motor unit potentials in all muscles tested. Muscle biopsy showed type 2 fiber atrophy and “minicores” in 30% of fibers. The minicores were characterized by small, well-circumscribed areas with reduction of oxidative staining, affecting both type 1 and type 2 fibers (Fig. 1). Genetic testing revealed compound heterozygous DOK7 mutations (S45L/1124_1127dupTGCC). We diagnosed LG-CMS, but no beneficial response to pyridostigmine was observed, and ephedrine was not tolerated. Albuterol (6 mg/day) was administered with improvement of strength and daily activities. Congenital myopathies are an important differential diagnosis in CMS. The pathological changes on light microscopy in CMS cases may lead to an erroneous diagnosis of congenital myopathy because muscle histology often shows non-specific myopathic changes in these disorders. In addition, as specific treatment exists for LGCMS, the patient with an erroneous diagnosis of congenital myopathy may not have access to proper treatment. The previous finding of minicores in 1 patient with LG-CMS and core-like areas in another, both with confirmed DOK7 mutations, has expanded the spectrum of pathological features in LG-CMS with DOK7 mutations. On electron microscopy, minicores present as areas of myofibrillar disruption and paucity of mitochondria, often with degeneration of the sarcomeres, structural changes of the sarcoplasmic reticulum and transverse
DOAJ (DOAJ: Directory of Open Access Journals), May 1, 2013
Pompe disease (PD) can be diagnosed by measuring alpha-glucosidase levels or by identifying mutat... more Pompe disease (PD) can be diagnosed by measuring alpha-glucosidase levels or by identifying mutations in the gene enzyme. Muscle biopsies can aid diagnosis in doubtful cases. Methods: A review of muscle biopsy from 19 cases of PD (infantile, 6 cases; childhood, 4 cases; and juvenile/adult, 9 cases). Results: Vacuoles with or without glycogen storage were found in 18 cases. All cases had increased acid phosphatase activity. The vacuole frequency varied (almost all fibers in the infantile form to only a few in the juvenile/adult form). Atrophy of type 1 and 2 fibers was frequent in all forms. Atrophic angular fibers in the NADH-tetrazolium reductase and nonspecific esterase activity were observed in 4/9 of the juvenile/adult cases. Conclusion: Increased acid phosphatase activity and vacuoles were the primary findings. Most vacuoles were filled with glycogen, and the adult form of the disease had fewer fibers with vacuoles than the infantile or childhood forms.<br>O diagn&#243;stico da doen&#231;a de Pompe (PD) pode ser feito pela dosagem da enzima alfa-glicosidase ou pela muta&#231;&#227;o do seu gene codificador. A bi&#243;psia muscular pode ajudar em casos duvidosos. M&#233;todos: Revis&#227;o das bi&#243;psias musculares de 19 casos de PD (forma infantil, 6 casos; infantil tardia, 4; e juvenil/adulto, 9). Resultados: Encontrados vac&#250;olos em 18 casos, com ou sem dep&#243;sito de glicog&#234;nio. Todos mostraram aumento da fosfatase &#225;cida. Os vac&#250;olos estavam presentes na maioria das fibras nas formas infantis, menos frequentes nas formas juvenil e mais raros nas formas do adulto. A atrofia de fibras dos tipos 1 e 2 ocorreram em todas as formas. Fibras atr&#243;ficas na NADH-tetrazolium redutase e esterase n&#227;o espec&#237;fica foram observadas em 4/9 das formas infantil tardia/adulta. Conclus&#245;es: Os dados mais frequentes foram vac&#250;olos, preenchidos por glicog&#234;nio com atividade aumentada da fosfatase &#225;cida. A forma adulta apresenta menor n&#250;mero de vac&#250;olos que [...]
OBJECTIVE: To analyze a series of patients with neuromyotonia from neuromuscular disorders unit, ... more OBJECTIVE: To analyze a series of patients with neuromyotonia from neuromuscular disorders unit, Hospital de Clinicas da Universidade Federal do Parana. BACKGROUND: Neuromyotonia is a rare disease characterized by spontaneous and continuous muscle activity due to a disorder of the peripheral nerve hyperexcitability. Patients develop persistent muscle contraction, classically worsening after exercise. Electromyography is characterized by neuromyotonic discharges and about 40% of patients have detectable voltage-gated potassium-channel (VGKC) antibodies. DESIGN/METHODS: We studied four patients with neuromyotonia, regarding the clinical, electrophysiological and immunological findings. RESULTS: The average age of onset of symptoms was 17.5 (7-35) years and there was no gender predilection. The average time between onset of symptoms and diagnosis was 9.5 (1-29) years. The patients had muscle twitching (100%), muscle hypertrophy and hyperhidrosis (100%), muscle cramps and stiffness (75%), pseudomyotonia (25%), weakness (75%), paresthesias (25%), dysphonia, dysphagia and dyspnea (25%) and central nervous system symptoms (25%). Family history and exogenous intoxication were negative. All patients had the dosage of anti-VGKC negative. Electrophysiological findings: myokymia and neuromyotonic discharges were found in all patients, douplets and multiplets in 100% and triplets in 50% of cases. The maximum intraburst frequency ranged from 70 to 200 Hz. Three patients were treated with carbamazepine and gabapentin with a good response to treatment. Three used phenytoin, and of these, two had a partial response and one had intolerance to the drug. One patient had epilepsy, one patient developed ulcerative colitis idiopathic, glomerulonephritis and eczema on the face and another one hypothyroidism, arthralgia and myalgia. CONCLUSIONS: The diagnosis of neuromyotonia is accomplished primarily through clinical and electrophysiological findings. Electromyography often confirms diagnosis by the presence of neuromyotonic discharges. The dosage of anti-CKVD has a low sensitivity for the diagnosis of disease. The association with autoimmune diseases can be observed, as described in this series. Disclosure: Dr. Scola has received personal compensation for activities with Merck Serono as scientific advisor board. Dr. Paranhos has nothing to disclose. Dr. Lorenzoni has nothing to disclose. Dr. Kay has nothing to disclose. Dr. Vincent has received personal compensation for activities with Athena Diagnostics. Dr. Vincent has received royalty payments from Athena Diagnostics. Dr. Werneck has nothing to disclose.
Background: The most prevalent autoimmune diseases (AID) of the Central Nervous System (CNS) are ... more Background: The most prevalent autoimmune diseases (AID) of the Central Nervous System (CNS) are Multiple Sclerosis (MS) and Neuromyelitis Optica Spectrum Disorder (NMOSD), both being demyelinating diseases. Recent studies show that patients with CNS demyelinating diseases have a higher risk of presenting associated diagnosis of another AIDs. Objectives: The present study aimed to evaluate the frequency of autoimmune comorbidities and autoantibodies in patients with MS and NMOSD. Design and setting: Were analyzed the medical records of 126 patients with MS or NMOSD, from the Demyelinating Diseases Outpatient Clinic in the Neurological and Psychiatric Unit in the Complexo Hospital de Clinicas da Universidade Federal do Parana (CHC-UFPR), taking in consideration the presence of AIDs and autoantibodies. Methods: The variables were organized in a Microsoft® Office Excel spreadsheet for statistical analysis. Results: Of the 126 analyzed cases, 111 (88%) corresponded to MS and 15 (12%) to NMOSD. From the total, at least one AID was associated in 11 patients (8.7%), six of which were diagnosed with MS and five with NMOSD (p&amp;lt;0.05). Regarding autoantibodies, there were 21 cases (16.7%) in which antinuclear antibodies (ANA) were present, and 12 cases (9.5%) in which autoantibodies other than ANA were present (p&amp;lt;0.05). Conclusions: The results of the study showed a higher frequency of AIDs in patients with CNS demyelinating diseases compared to the normal population. The results found in this study may contribute to improve the treatment and follow-up of patients with CNS demyelinating diseases, so that the concomitance of other AIDs is considered by the clinician.
Necrotizing myopathy (NM) can occur with drug abuse, use of toxic agents, autoimmune diseases, an... more Necrotizing myopathy (NM) can occur with drug abuse, use of toxic agents, autoimmune diseases, and neoplasia. The aim of this report is to demonstrate that NM can be the first manifestation of human immunodeficiency virus (HIV) infection. A 20-year-old man presented with progressive proximal weakness and diffuse myalgias for 1 month, associated with fever and lymphadenopathy for most of this time. He denied use of statins or illicit drugs. He had a temperature of 37.88C, lymphadenopathy, diffuse edema, bilateral peripheral facial palsy, nasal voice, impaired palate elevation, limb hypotonia, and proximal weakness in the upper and lower limbs [Medical Research Council (MRC) grade 3]. Laboratory tests on admission showed creatine kinase of 26,167 U/L (normal 30–200 U/L), C-reactive protein of 2.76 mg/dl (normal <0.5 mg/dl), positive HIV serology, CD4 count of 300 cells/mm, CD4/CD8 ratio of 0.7, and viral load of 50,027 copies. Anti-nuclear antibody titers and serological tests for hepatitis, cytomegalovirus, toxoplasmosis, syphilis, and Epstein–Barr virus were negative. Nerve conduction studies were normal. Needle electromyography revealed fibrillation potentials and polyphasic motor unit potentials of short duration and low amplitude in the brachial biceps muscle. MRI showed hyperintensity in short-tau inversion recovery (STIR)–weighted images and mild contrast enhancement in the brachial biceps and vastus lateralis muscles. Muscle biopsy was suggestive of NM (Fig. 1). Therapy was initiated with antiretroviral drugs and prednisone 60 mg/day. After 1 month of therapy, weakness worsened (MRC grade 2), and CK levels remained elevated (17,220 U/L). Intravenous immunoglobulin (400 mg/kg/day for 5 days) was administered, which resulted in marked and progressive improvement of weakness. Evaluation 1 month later revealed a CK of 139 U/L, CD4 count of 1,179 cells/mm, CD4/CD8 ratio 1.66, and an undetectable viral load. After 2 years of treatment, the patient was asymptomatic on antiretroviral therapy. Myalgias and weakness are common symptoms in HIV patients during all stages of disease and may be due to viremia, antiretroviral therapy, or myopathy associated with the virus. Histological studies have demonstrated that muscle involvement in HIV is more common than previously suspected. Reports of NM associated with HIV are rare, and have occurred in chronic HIV patients, some of whom were treated with antiretroviral drugs. Our patient had NM as the initial manifestation of HIV infection. NM should be differentiated from other myopathies related to HIV, because it is potentially reversible with treatment. The definitive test for diagnosis of NM is muscle biopsy, which shows necrotic and regenerating muscle fibers with no or mild inflammation. Membrane attack complex deposition may also be present in small vessels and/or muscle fibers, and major histocompatibility complex class 1 (MHC 1) may be upregulated. The patient showed improvement after treatment with intravenous immunoglobulin. There is little information about the importance of antiretroviral therapy in patients with NM and HIV, but in this patient the antiretroviral treatment did not lead to rapid improvement in the myopathy. Although this patient did improve, the prognosis of NM associated with HIV remains unknown.
Treatment of multiple sclerosis (MS) has progressed significantly in recent years and now include... more Treatment of multiple sclerosis (MS) has progressed significantly in recent years and now includes immunosuppressants, immunomodulators, biologics and, more recently, medications that interfere with the release or maturation of lymphocytes. These medications have been shown to reduce the number of relapses, but the results in terms of reduced disability have been modest as most of the studies carried out were generally restricted to two years 1,2. Since the introduction of immunomodulators to treat MS, the response has been found to vary from patient to patient and with the research center where the study was conducted 3. To find a factor that influences the evolution of MS in patients treated with disease modifying therapies (DMTs), several
Greenfield, em 1933, relatou os casos de duas crianças que evoluíram normalmente até o segundo an... more Greenfield, em 1933, relatou os casos de duas crianças que evoluíram normalmente até o segundo ano de vida e que, progressivamente, perderam a capacidade para deambular, acompanhada de déficit intelectual, arreflexia, hipotonia muscular, sinais de envolvimento de tratos longos com atitudes de descerebração no final da vida, cuja característica patológica era o desaparecimento da oligodendroglia interfascicular •™. Em 1938, Einarson e Neel notaram que esta forma de esclerose cerebral se corava metaci omaticamente com corantes básicos da anilina e, em 1942, utilizaram pela primeira vez o termo leucoencefalopatia metacromática 11. Em 1950, Brain e Greenfield sugeriram que a metacromasia da leucoencefalopatia metacromática era devida ao acúmulo de ésteres do ácido sulfürico 20 , mas foi somente Jatskewitz, em 1958, que demonstrou serem na verdade sulfatídeos 42. Austin, em 1957, revelava que estas substâncias também estavam presentes em outros órgãos fora do sistema nervoso, como, por exemplo, o rim 3 » 4. Em 1963, Austin e col. 7 « !, » 10 e Mehl e Jatskewitz 40 , demonstraram que na leucodistrofia metacromática existia deficiência de arilsulfatase A, uma enzima que regula o metabolismo dos sulfatídeos, transformando-os em cerebrosídeos, o que seria a causa da doença. Tivemos a oportunidade de estudar dois pacientes que apresentavam leucodistrofia metacromática. Pela raridade de casos descritos no Brasil e para difundir os métodos empregados no diagnóstico, julgamos válido este relato. OBSERVAÇÕES Caso 1-IFB, sexo feminino, cor branca, 2 anos e 10 meses. Nascida de gestação e parto normais, controlou a cabeça aos três meses, sentou aos cinco meses e engatinhou aos oito meses. Andou com dezoito meses e falou com 24 meses. Nfto chegou a controlar os esfintercs. Logo após iniciar a marcha sem auxilio passou a ter dificuldade
RESUMO-Os autores relatam um caso de plexopatia lombossacra em criança e em que a extensa investi... more RESUMO-Os autores relatam um caso de plexopatia lombossacra em criança e em que a extensa investigação, incluindo ressonância nuclear magnética normal, biópsia muscular compatível com desinervação inicial e eletromiografia normal, afastou condições associadas. O paciente apresentava dor intensa, fraqueza e atrofia do membro inferior esquerdo, reflexo aquileu ausente e reflexo patelar diminuído à esquerda. Parestesia no membro envolvido acompanhava o quadro. O tratamento realizado foi dexametasona por um mês e morfina intratecal durante três meses. A evolução foi favorável, apresentando, após um ano, atrofia discreta do membro acometido e leve paresia do músculo iliopsoas esquerdo. PALAVRAS-CHAVE: plexo lombossacro, neuropatía, idiopatia. Idiopathic lumbosacral plexus neuropathy in childhood: case report ABSTRACT-We describe a lumbosacral plexus neuropathy case in childhood in which detailed investigation, including eletromyography and magnetic resonance imaging, was normal. Muscle biopsy showed mild denervation. No underlyng condition was detected. The patient presented with pain, weakness and light atrophy in left lower limb, reduced reflex at the ankle, loss of the quadriceps reflex and paresthesy in involved limb. Recovery after one year was almost complete, with persistent slight weakness and atrophy.
OBJECTIVE: To analyze a series of patients with neuromyotonia from neuromuscular disorders unit, ... more OBJECTIVE: To analyze a series of patients with neuromyotonia from neuromuscular disorders unit, Hospital de Clinicas da Universidade Federal do Parana. BACKGROUND: Neuromyotonia is a rare disease characterized by spontaneous and continuous muscle activity due to a disorder of the peripheral nerve hyperexcitability. Patients develop persistent muscle contraction, classically worsening after exercise. Electromyography is characterized by neuromyotonic discharges and about 40% of patients have detectable voltage-gated potassium-channel (VGKC) antibodies. DESIGN/METHODS: We studied four patients with neuromyotonia, regarding the clinical, electrophysiological and immunological findings. RESULTS: The average age of onset of symptoms was 17.5 (7-35) years and there was no gender predilection. The average time between onset of symptoms and diagnosis was 9.5 (1-29) years. The patients had muscle twitching (100%), muscle hypertrophy and hyperhidrosis (100%), muscle cramps and stiffness (75%), pseudomyotonia (25%), weakness (75%), paresthesias (25%), dysphonia, dysphagia and dyspnea (25%) and central nervous system symptoms (25%). Family history and exogenous intoxication were negative. All patients had the dosage of anti-VGKC negative. Electrophysiological findings: myokymia and neuromyotonic discharges were found in all patients, douplets and multiplets in 100% and triplets in 50% of cases. The maximum intraburst frequency ranged from 70 to 200 Hz. Three patients were treated with carbamazepine and gabapentin with a good response to treatment. Three used phenytoin, and of these, two had a partial response and one had intolerance to the drug. One patient had epilepsy, one patient developed ulcerative colitis idiopathic, glomerulonephritis and eczema on the face and another one hypothyroidism, arthralgia and myalgia. CONCLUSIONS: The diagnosis of neuromyotonia is accomplished primarily through clinical and electrophysiological findings. Electromyography often confirms diagnosis by the presence of neuromyotonic discharges. The dosage of anti-CKVD has a low sensitivity for the diagnosis of disease. The association with autoimmune diseases can be observed, as described in this series. Disclosure: Dr. Scola has received personal compensation for activities with Merck Serono as scientific advisor board. Dr. Paranhos has nothing to disclose. Dr. Lorenzoni has nothing to disclose. Dr. Kay has nothing to disclose. Dr. Vincent has received personal compensation for activities with Athena Diagnostics. Dr. Vincent has received royalty payments from Athena Diagnostics. Dr. Werneck has nothing to disclose.
Background: Polyneuropathies are characterized by a symmetrical impairment of the peripheral nerv... more Background: Polyneuropathies are characterized by a symmetrical impairment of the peripheral nervous system, resulting in sensory, motor and/or autonomic deficits. Due to the heterogeneity of causes, an etiological diagnosis for polyneuropathy is challenging. Objective: The aim of this study was to determine the main causes of polyneuropathy confirmed by electrodiagnostic (EDX) tests in a tertiary service and its neurophysiological aspects. Methods: This observational cross-sectional study from a neuromuscular disorders center included individuals whose electrodiagnostic tests performed between 2008 and 2017 confirmed a diagnosis of polyneuropathy. Through analysis of medical records, polyneuropathies were classified according to etiology and neurophysiological aspect. Results: Of the 380 included patients, 59.5% were male, with a median age of 43 years. The main etiologies were: inflammatory (23.7%), hereditary (18.9%), idiopathic (13.7%), multifactorial (11.1%), and diabetes (10.8...
Background: The peripheral polyneuropathies have etiological heterogeneity, with more than a hund... more Background: The peripheral polyneuropathies have etiological heterogeneity, with more than a hundred known causes. In addition, they have a lack of information related to their epidemiology. Objectives: The aim of this study is to determine the prevalence of each etiology of polyneuropathy in a single specialized center from Southern Brazil and to correlate main clinical manifestations and electrophysiological aspects. Design and setting: Observational cross-sectional study. Neuromuscular disorder center from a tertiary service. Methods: This study comprised individuals with electrodiagnostic tests compatible with polyneuropathy from a neuromuscular disorder center. Selected patients were those who underwent nerve conduction studies between 2008 and 2017. Through analysis of medical records, polyneuropathies were classified according to etiology and neurophysiological aspect. Results: The sample population consisted of 380 patients who has a male predominance (59.5%), with a median ...
N euromyelitis optica (NMO) is a rare autoimmune disorder of the central nervous system that main... more N euromyelitis optica (NMO) is a rare autoimmune disorder of the central nervous system that mainly affects the optic nerves and spinal cord related with serum autoantibodies to aquaporin-4 (1). In addition, the term “astrocytopathy” has been proposed because histopathological studies have shown that astrocyte injury is the primary event, which occurs in the active lesions of NMO (2). In 1894, on the Congrès Français de Médecine in Lyon, Eugène Devic (1858–1930) presented an article in which he called the disease “neuro-myélite optique aiguë.” In the same year, Devic’s student Fernand Gault (1873–1936) published his doctoral thesis, entitled “De la neuro-myélite optique aiguë.” Gault’s work is commonly considered to be the first review of NMO, and the disease was named after Devic in 1907 (3–5). However, previously in 1870, in his famous lecture On the Ophthalmoscopic Signs of Spinal Disease (6), Thomas Clifford Allbutt (Fig. 1) briefly mentioned a patient with acute myelitis and “a sympathetic eye disorder.” This case is considered the first account of a patient with NMO in the literature. Apart from the phylogenetic discussion of the NMO, the work of Professor Allbutt allowed us to deepen the theme by engaging the importance of ophthalmological evaluation in neurology.
We reported one patient with Charcot-Marie-Tooth type 4C (CMT4C) who developed seropositive myast... more We reported one patient with Charcot-Marie-Tooth type 4C (CMT4C) who developed seropositive myasthenia gravis. Neuromuscular junction alterations in CMT4C patients have not yet been reported. However, few patients have been reported to simultaneously have MG and CMT, but none with CMT4C. Our report suggests that additional research is required to confirm whether genetic neuropathies may predispose to MG.
In 1951, the physiologist George Duncan Dawson presented his work with the averaging of the signa... more In 1951, the physiologist George Duncan Dawson presented his work with the averaging of the signal in the evoked potentials (EPs), opening a new stage in the development of clinical neurophysiology. The authors present aspects of Professor Dawson’s biography and a review of his work on the EPs and, mainly, the article reveals the new technique in detail that would allow the growth of the clinical application of the visual, auditory, and somatosensory EPs.
This paper reviews some aspects of the life and work of Professor Johann Friedrich Horner, on the... more This paper reviews some aspects of the life and work of Professor Johann Friedrich Horner, on the occasion of the 190th anniversary of his birthday and 152 years after the publication of "Über eine Form von Ptosis". It also shows the importance of the historical description of ptosis, myosis and anhidrosis associating those symptoms with sympathetic cervical damage. He pharmacologically confirmed the impairment of sympathetic innervation to the eye and preserved parasympathetic function.
Congenital myasthenic syndromes (CMS) are heterogeneous genetic diseases in which neuromuscular t... more Congenital myasthenic syndromes (CMS) are heterogeneous genetic diseases in which neuromuscular transmission is compromised. CMS resembling the Lambert-Eaton myasthenic syndrome (CMS-LEMS) are emerging as a rare group of distinct presynaptic CMS that share the same electrophysiological features. They have low compound muscular action potential amplitude that increment after brief exercise (facilitation) or high-frequency repetitive nerve stimulation. Although clinical signs similar to LEMS can be present, the main hallmark is the electrophysiological findings, which are identical to autoimmune LEMS. CMS-LEMS occurs due to deficits in acetylcholine vesicle release caused by dysfunction of different components in its pathway. To date, the genes that have been associated with CMS-LEMS are AGRN, SYT2, MUNC13-1, VAMP1, and LAMA5. Clinicians should keep in mind these newest subtypes of CMS-LEMS to achieve the correct diagnosis and therapy. We believe that CMS-LEMS must be included as an important diagnostic clue to genetic investigation in the diagnostic algorithms to CMS. We briefly review the main features of CMS-LEMS.
Children with a congenital myasthenic syndrome (CMS) who present with fatigability or weakness wi... more Children with a congenital myasthenic syndrome (CMS) who present with fatigability or weakness with symptoms confined to a limb-girdle distribution may be easily mistaken for having a congenital myopathy or muscular dystrophy. We report a patient with limb-girdle CMS (LG-CMS) due to a DOK7 mutation who presented with minicore areas in her muscle biopsy. A 10-year-old girl, born prematurely, presented with respiratory difficulty since birth. At 6 years of age she had progressive weakness that first affected the proximal muscles in the arms and legs, and changed according to physical activity. There were no delayed motor milestones or relatives with similar symptoms. On neurological examination she had mild symmetrical eyelid ptosis and facial weakness, mild proximal muscle atrophy in the arms, scapular winging, symmetrical proximal weakness in the arms [Medical Research Council (MRC) grade 3] and legs (MRC grade 4), axial muscle weakness with scoliosis and lordosis, and reduced tendon reflexes in the arms. The initial diagnosis was CMS or congenital myopathy, but serum creatine kinase levels were normal. Repetitive nerve stimulation showed >10% decrement in the musculocutaneous and spinal accessory nerves but no decrement in the facial, ulnar, or median nerves. Needle electromyography revealed low-amplitude, short-duration motor unit potentials in all muscles tested. Muscle biopsy showed type 2 fiber atrophy and “minicores” in 30% of fibers. The minicores were characterized by small, well-circumscribed areas with reduction of oxidative staining, affecting both type 1 and type 2 fibers (Fig. 1). Genetic testing revealed compound heterozygous DOK7 mutations (S45L/1124_1127dupTGCC). We diagnosed LG-CMS, but no beneficial response to pyridostigmine was observed, and ephedrine was not tolerated. Albuterol (6 mg/day) was administered with improvement of strength and daily activities. Congenital myopathies are an important differential diagnosis in CMS. The pathological changes on light microscopy in CMS cases may lead to an erroneous diagnosis of congenital myopathy because muscle histology often shows non-specific myopathic changes in these disorders. In addition, as specific treatment exists for LGCMS, the patient with an erroneous diagnosis of congenital myopathy may not have access to proper treatment. The previous finding of minicores in 1 patient with LG-CMS and core-like areas in another, both with confirmed DOK7 mutations, has expanded the spectrum of pathological features in LG-CMS with DOK7 mutations. On electron microscopy, minicores present as areas of myofibrillar disruption and paucity of mitochondria, often with degeneration of the sarcomeres, structural changes of the sarcoplasmic reticulum and transverse
DOAJ (DOAJ: Directory of Open Access Journals), May 1, 2013
Pompe disease (PD) can be diagnosed by measuring alpha-glucosidase levels or by identifying mutat... more Pompe disease (PD) can be diagnosed by measuring alpha-glucosidase levels or by identifying mutations in the gene enzyme. Muscle biopsies can aid diagnosis in doubtful cases. Methods: A review of muscle biopsy from 19 cases of PD (infantile, 6 cases; childhood, 4 cases; and juvenile/adult, 9 cases). Results: Vacuoles with or without glycogen storage were found in 18 cases. All cases had increased acid phosphatase activity. The vacuole frequency varied (almost all fibers in the infantile form to only a few in the juvenile/adult form). Atrophy of type 1 and 2 fibers was frequent in all forms. Atrophic angular fibers in the NADH-tetrazolium reductase and nonspecific esterase activity were observed in 4/9 of the juvenile/adult cases. Conclusion: Increased acid phosphatase activity and vacuoles were the primary findings. Most vacuoles were filled with glycogen, and the adult form of the disease had fewer fibers with vacuoles than the infantile or childhood forms.<br>O diagn&#243;stico da doen&#231;a de Pompe (PD) pode ser feito pela dosagem da enzima alfa-glicosidase ou pela muta&#231;&#227;o do seu gene codificador. A bi&#243;psia muscular pode ajudar em casos duvidosos. M&#233;todos: Revis&#227;o das bi&#243;psias musculares de 19 casos de PD (forma infantil, 6 casos; infantil tardia, 4; e juvenil/adulto, 9). Resultados: Encontrados vac&#250;olos em 18 casos, com ou sem dep&#243;sito de glicog&#234;nio. Todos mostraram aumento da fosfatase &#225;cida. Os vac&#250;olos estavam presentes na maioria das fibras nas formas infantis, menos frequentes nas formas juvenil e mais raros nas formas do adulto. A atrofia de fibras dos tipos 1 e 2 ocorreram em todas as formas. Fibras atr&#243;ficas na NADH-tetrazolium redutase e esterase n&#227;o espec&#237;fica foram observadas em 4/9 das formas infantil tardia/adulta. Conclus&#245;es: Os dados mais frequentes foram vac&#250;olos, preenchidos por glicog&#234;nio com atividade aumentada da fosfatase &#225;cida. A forma adulta apresenta menor n&#250;mero de vac&#250;olos que [...]
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