Ultra-high dose of intravenous immunoglobulin restores strength and motor function in a patient with refractory multifocal motor neuropathy. / Dosis ultraaltas de inmunoglobulina endovenosa mejoran la fuerza y la funcionalidad motora en una paciente con neuropatía motora multifocal refractaria.

INTRODUCTION: Multifocal motor neuropathy (MMN) is a chronic progressive immune-mediated neuropathy, predominantly involving upper limbs asymmetrically with electrophysiologic evidence of motor conduction block. The treatment of choice is immunoglobulin (Ig). Nevertheless, some patients may become resistant to treatment. We describe a patient with history of MMN who became resistant to gammaglobulin treatment but markedly improved using ultra-high doses of intravenous immunoglobulin. CASE REPORT: A 36-year-old woman with diagnosis of MMN. After 5 years of clinical stability under subcutaneous Ig (2g/kg/month) the patient developed bilateral weakness involving both hands. Treatment was switched to intravenous Ig 2g/kg/month, nevertheless, she progressed and became totally dependent for activities of daily living. We started ultra-high dose intravenous immunoglobulin 5 g/kg/month, with good response. She became independent for activities of daily living and returned to work. The only treatment related adverse event was headache during infusion. CONCLUSION: Ultra-high dose intravenous Ig seems to be a useful therapy in aggressive MMN with severe disability despite conventional treatment. A low cardiovascular risk score (QRISK2 less than 10%) and a daily intravenous Ig lower than 35 g reduce the risk of severe complications related to intravenous Ig.

TITLE: Dosis ultraaltas de inmunoglobulina endovenosa mejoran la fuerza y la funcionalidad motora en una paciente con neuropatía motora multifocal refractaria.Introducción. La neuropatía motora multifocal (NMM) es una enfermedad crónica, progresiva e inmunomediada que afecta predominantemente a los miembros superiores de forma asimétrica. En los estudios electrofisiológicos se evidencian bloqueos en la conducción motora, y el tratamiento de elección es la inmunoglobulina humana (Ig); sin embargo, algunos pacientes pueden desarrollar refractariedad a este tratamiento. Describimos el caso de una paciente con diagnóstico de NMM que desarrolló refractariedad a la gammaglobulina y que mejoró marcadamente con dosis ultraaltas de esta misma medicación. Caso clínico. Mujer de 36 años, con diagnóstico de NMM, que, después de cinco años de estabilidad clínica bajo tratamiento con Ig subcutánea en dosis de 2 g/kg/mes, evolucionó con grave debilidad en ambas manos, por lo que se decidió cambiar el tratamiento a Ig endovenosa. No obstante, progresó hasta quedar incapacitada para realizar actividades básicas de la vida diaria. Iniciamos tratamiento con Ig endovenosa en dosis ultraaltas (5 g/kg/mes) con buena respuesta, logrando independencia funcional en las actividades de la vida diaria y que regresara al trabajo. El único evento adverso relacionado con la Ig endovenosa en dosis ultraaltas fue la presencia de cefalea durante la infusión. Conclusión. La Ig endovenosa en dosis ultraaltas parece ser un tratamiento efectivo para pacientes con NMM y grave discapacidad no respondedores a dosis convencionales. Un bajo índice de riesgo cardiovascular (QRISK2 menor que 10%) y una dosis diaria de Ig endovenosa menor de 35 g reducen el riesgo de complicaciones graves relacionadas con el uso de esta medicación.

Brain MRI findings in children and adolescents with Fabry disease.

OBJECTIVE: To evaluate the presence of white matter and hemorrhagic lesions in brain MRI of children and adolescents with Fabry disease (FD). METHODS: Brain MRI studies in 44 consecutive children and teenagers (20 boys, mean age 14.6 years, range 7-21 years) were evaluated using classic sequences as well as, GRE-weighted images, for white matter lesions (WML) and chronic microbleed detection. All patients lacked history of stroke or TIA. Brain MRI findings in 46 consecutive children and adolescents without FD, referred for the evaluation of headaches (36 females, mean age 14.1 years, range 7-21 years) were evaluated as a control group. Additionally, we assessed the clinical manifestations of FD. RESULTS: Seven children (15.9%) with FD had brain MRI evidence of asymptomatic WML (5 girls, mean age 14.8 years, range: 13-20 years) compared with 3 children (6.5%) in the control group (p = 0.01). Brain abnormalities in patients with FD revealed WML, deep gray matter and infratentorial involvement. Three patients presented two lesions each. None of the children showed microbleeds. Regarding clinical manifestations, 90.9% of the patients had signs or symptoms of FD. CONCLUSION: We identified asymptomatic white matter brain lesions in 15.9% of children with FD without clinical history of stroke. FD is a treatable disorder that should be routinely included in the differential diagnosis of both symptomatic and asymptomatic brain lesions in children and adolescents. The detection of brain lesions may foster earlier treatment.

Electric vs magnetic trans-cranial stimulation of the brain in healthy humans: a comparative study of central motor tracts 'conductivity' and 'excitability'.

Motor evoked potentials (MEPs) were elicited in the thenar muscles of 11 healthy volunteers via individual electric unifocal and magnetic trans-cranial stimuli (TCS). The effects of TCS strength, of the muscular state (relaxed, contracted) as well as of the amplitude-latency characteristics and the duration of the motor tracts central conduction times (CCTs) to hand muscles, were evaluated and compared between the two types of brain excitation. MEPs with the shortest latency (18.91 +/- 1.31 ms) were recorded in the voluntarily contracted muscle during electric TCS, whilst those with maximal latency (23.3 +/- 1.63 ms) were found after magnetic TCS with an intensity at threshold for eliciting an MEP of about 0.1 mV in the relaxed muscle. Mean CCTs for electric and magnetic TCS calculated in the contracted target muscles, were respectively 5.07 +/- 0.51 and 6.34 +/- 0.46 ms. MEPs with larger amplitudes and durations were observed during magnetic TCS, being maximal when suprathreshold stimuli were delivered. A restricted range of liminar values of magnetic TCS was obtained by defining the threshold for raising motor responses in complete muscle relaxation, indicating that magnetic pulses might represent a useful probe for testing the 'excitability' of the motor tracts.

[Sun rays diaphragm: an ultrasonographic sign of interstitial involvement in the base of the lung]. / Diafragma en rayos de sol: signo ecográfico de afectación intersticial de la base pulmonar.

OBJECTIVES: The purpose of this article is to present a new ultrasonographic sign: the spiculated diaphragm or sun rays diaphragm, that makes it possible to suspect disease in the base of the lung, generally involving the subpleural interstitium, during abdominal ultrasound examination. MATERIAL AND METHODS: We present a study of seven patients in whom the diaphragm was observed as an echogenic, curvilinear, thickened image with numerous echogenic vertical lines or bands radiating from it posteriorly during abdominal ultrasound examination using a sectorial transducer. We have named this spiculated appearance of the diaphragm sun rays diaphragm. All patients underwent posteroanterior and lateral plain-film chest x-rays and high-resolution chest computed tomography (CT) with slices of the bases of the lungs. RESULTS: The chest pathology responsible for this finding was pulmonary fibrosis (n = 2), mitral valulopathy with heart failure (n = 2), unilateral atresia of the pulmonary vein (n = 1); combined miliary tuberculosis and Pneumocystis infection in an AIDS patient (n = 1), and carcinomatous lymphangitis (n = 1). CONCLUSIONS: When a spiculated or sun rays diaphragm is observed during abdominal ultrasonography, disease involving the base of the lung (generally the subpleural interstitium) should be suspected; thus, in the absence of prior clinical knowledge of lung disease, additional examinations such as plain-film chest x-rays or thin slice chest CT should be performed.

Periodic limb movements in syringomyelia and syringobulbia.

Twenty-six patients with syringomyelia were studied with polysomnography to determine the frequency of periodic limb movements (PLM) and its relationship to the presence of a Chiari anomaly, the severity of corticospinal tract involvement, and localization of the syrinx. Sixteen patients showed PLM in stages I and II of non-REM sleep and three PLM also while awake. There were no statistically significant differences in overall disability, corticospinal signs, presence of an associated Chiari anomaly, and disease duration between patients with and without PLM, although there was a trend for patients with PLM to have more severe disease. There was preservation of the lumbosacral enlargement of the spinal cord by the syrinx in all patients with PLM. The latency delay between lower and upper limb muscles was suggestive of conduction along propriospinal pathways. Syringomyelia may lead to an abnormal state of spinal hyperexcitability favoring the appearance of PLM. Detailed magnetic resonance image studies of patients with different localizations of the syrinx cavities may help to determine which tracts are involved in the production of PLM.

SEPs and CNS magnetic stimulation in syringomyelia.

Somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) to transcranial and spinal stimulation from upper and lower limb muscles were elicited in 13 patients with syringomyelia. Seven had an associated Chiari type I anomaly. Diagnosis was confirmed by MRI. In 5 cases, SEPs and MEPs were performed before and after surgical treatment. Prolonged central motor conduction times or absent motor responses in upper or lower limbs were found in most patients. The greatest number of abnormalities was disclosed by measurement of CMCT followed by SEPs after tibial nerve stimulation. Two of 5 cases undergoing surgery improved clinically and showed reduction in CMCT after surgical treatment. Our study shows that MEPs were useful in the evaluation of neurophysiological status in syringomyelia patients, helping to estimate anterolateral spinal cord function.

Amyotrophic lateral sclerosis IgG-treated neuromuscular junctions develop sensitivity to L-type calcium channel blocker.

In order to search for early changes induced by the application of human immunoglobulin G (IgG) on motor nerve terminals, IgG from patients with amyotrophic lateral sclerosis (ALS) and control subjects was injected subcutaneously into the levator auris muscle of mice. A week or a month after the last injection, endplate potentials were recorded. No changes in quantal content of transmitter release were observed. In control and ALS IgG-treated muscles, neurotransmitter release remained sensitive to P/Q-type and insensitive to N-type voltage-sensitive calcium channel (VSCC) blockers as in untreated muscles. In contrast, IgG from 5 of 8 different ALS patients induced a significant reduction in quantal content of the evoked response after incubation with nitrendipine, indicating that a novel sensitivity to this calcium channel blocker appears in these motor nerve terminals. These results indicate that ALS IgG induces plastic changes at nerve terminals. The expression of transmitter release coupled to L-type VSCC indicate that ALS IgGs are capable of inducing plastic changes at the nerve terminals that may participate in the process leading to neuronal death.

Focal stiff-person syndrome.

Stiff-person syndrome (SPS) is a disorder of motor function characterized by rigidity of axial musculature and fluctuating painful spasms, which are often induced by startle or emotional stimuli. Neurophysiological studies have demonstrated the presence of continuous motor unit activity in muscle at rest, with abnormally enhanced extereoceptive reflexes. Although criteria for the diagnosis of SPS were proposed, several variants of this syndrome have been described before. In this communication, we report the case of a patient with a focal form of SPS. A 39-year-old woman developed progressive instability in her gait, spasms and stiffness restricted to both legs. The electromyographic examination showed continuous motor unit activity of the affected muscles at rest. Moreover, high anti-GAD antibodies titers were found in CSF and serum. Clinical symptoms, electrophysiological and immunological profiles suggest a focal form of SPS. Clinical and immunological findings indicate that SPS is a heterogeneous disease, suggesting the need to redefine its diagnostic criteria. Definition of the range of clinical expression and immunological profiles could be important for the clinical management of these patients.

Playing harp, another unusual task-specific dystonia.

Herein we report a task-specific dystonia in a 48-year-old woman, with an unusual association between a familial harp-playing dystonia and essential tremor.

[Gastric pseudotumor caused by varices]. / Pseudotumor gástrico por varices.

A case is presented of a variceal gastric pseudotumor demonstrated by angiography. The literature is reviewed and the authors underline the importance of including varices in the differential diagnosis of submucosal gastric tumor.

Thyrotoxic periodic paralysis in caucasians. Report of 8 cases.

BACKGROUND: Periodic paralysis is a well known complication of thytotoxicosis in Chinese and Japanese patients, but has been considered extremely rare in caucasians. PATIENTS AND METHODS: Between 1991 and 1996, we admitted 8 caucasian patients to our Hospital due to thyrotoxic periodic paralysis. We retrospectively analysed their clinical manifestations. RESULTS: All the patients were males. Their attacks started at night or early after awakening, frequently triggered by a high carbohydrate diet and physical exertion. Myalgias and flaccid weakness predominated over proximal leg muscles, sparing bulbar and respiratory musculature. Reflexes were brisk at the onset of the attack and reduced or absent during the course of the episode. Prior to diagnosis patients presented 1-5 attacks of thyrotoxic periodic paralysis each lasting 1-96 hours. Hypokalemia was documented in 6 patients. The episodes of periodic paralysis led to the diagnosis of a previously unsuspected thyrotoxicosis in 6 patients. In the other 2 patients the diagnosis of the thyroid dysfunction preceded the periodic paralysis. Attacks resolved after treatment of the hyperthyroid state. CONCLUSIONS: Thyrotoxic periodic paralysis is an under-diagnosed but probably frequent complication of hyperthyroidism in caucasians. Early recognition of the attacks is essential to investigate and treat the underlying thyroid dysfucntion whose symptoms are usually mild. The episodes of periodic paralysis resolve with the correction of the hyperthyroidism.