RESUMEN
The identification of new variants of the stiff man syndrome (SMS) and of new, probably pathogenic neuronal autoantibodies has led to the concept of stiff man (or person) spectrum disorders (SPSD). This is an expanding group of rare chronic autoimmune inflammatory diseases of the central nervous system (CNS) that have in common the main symptoms of fluctuating rigidity and spasms with pronounced stimulus sensitivity. These core symptoms are mandatory and can be accompanied by a wide variety of other neurological signs. The SPSDs are associated with autoantibodies directed against neuronal proteins that attenuate excitability. Neither clinical phenotypes nor the course of SPSD correlate closely with the antibody status. The treatment of these diseases aims at maintaining mobility and is pragmatically oriented to the degree of impediment and comprises antispastic, anticonvulsant and immunomodulating or immunosuppressive medication strategies.
Asunto(s)
Síndrome de la Persona Rígida/diagnóstico , Autoanticuerpos/sangre , Enfermedades Autoinmunes/clasificación , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/terapia , Sistema Nervioso Central/inmunología , Correlación de Datos , Diagnóstico Diferencial , Encefalomielitis/clasificación , Encefalomielitis/diagnóstico , Encefalomielitis/inmunología , Encefalomielitis/terapia , Humanos , Rigidez Muscular/clasificación , Rigidez Muscular/diagnóstico , Rigidez Muscular/inmunología , Rigidez Muscular/terapia , Proteínas del Tejido Nervioso/inmunología , Pronóstico , Calidad de Vida , Síndrome de la Persona Rígida/clasificación , Síndrome de la Persona Rígida/inmunología , Síndrome de la Persona Rígida/terapiaRESUMEN
Myoclonus is often a diagnostic and therapeutic challenge due to its broad phenomenological variability and limited therapeutic options. This article gives a short survey and characterizes in detail two common types of myoclonus, cortical myoclonus and reticular reflex myoclonus. Clinical testing and electrophysiological investigations provide relevant local diagnostic indications for the generating structure(s). Such indications would influence not only the strategies of neuroimaging and laboratory investigations aimed at clarifying the underlying cause but also the selection of drugs to suppress myoclonus.
Asunto(s)
Mioclonía/diagnóstico , Anticonvulsivantes/uso terapéutico , Encefalopatías/diagnóstico , Encefalopatías/tratamiento farmacológico , Encefalopatías/etiología , Encefalopatías/fisiopatología , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/fisiopatología , Diagnóstico Diferencial , Epilepsias Mioclónicas/diagnóstico , Epilepsias Mioclónicas/diagnóstico por imagen , Epilepsias Mioclónicas/etiología , Epilepsias Mioclónicas/fisiopatología , Humanos , Hiperekplexia/diagnóstico , Hiperekplexia/tratamiento farmacológico , Hiperekplexia/fisiopatología , Trastornos del Movimiento/diagnóstico , Trastornos del Movimiento/fisiopatología , Mioclonía/tratamiento farmacológico , Mioclonía/etiología , Mioclonía/fisiopatología , Tegmento Pontino/efectos de los fármacos , Tegmento Pontino/fisiopatología , Formación Reticular/efectos de los fármacos , Formación Reticular/fisiopatologíaRESUMEN
The clinical associations of glycine receptor antibodies have not yet been described fully. We identified prospectively 52 antibody-positive patients and collated their clinical features, investigations and immunotherapy responses. Serum glycine receptor antibody endpoint titres ranged from 1:20 to 1:60 000. In 11 paired samples, serum levels were higher than (n = 10) or equal to (n = 1) cerebrospinal fluid levels; there was intrathecal synthesis of glycine receptor antibodies in each of the six pairs available for detailed study. Four patients also had high glutamic acid decarboxylase antibodies (>1000 U/ml), and one had high voltage-gated potassium channel-complex antibody (2442 pM). Seven patients with very low titres (<1:50) and unknown or alternative diagnoses were excluded from further study. Three of the remaining 45 patients had newly-identified thymomas and one had a lymphoma. Thirty-three patients were classified as progressive encephalomyelitis with rigidity and myoclonus, and two as stiff person syndrome; five had a limbic encephalitis or epileptic encephalopathy, two had brainstem features mainly, two had demyelinating optic neuropathies and one had an unclear diagnosis. Four patients (9%) died during the acute disease, but most showed marked improvement with immunotherapies. At most recent follow-up, (2-7 years, median 3 years, since first antibody detection), the median modified Rankin scale scores (excluding the four deaths) decreased from 5 at maximal severity to 1 (P < 0.0001), but relapses have occurred in five patients and a proportion are on reducing steroids or other maintenance immunotherapies as well as symptomatic treatments. The glycine receptor antibodies activated complement on glycine receptor-transfected human embryonic kidney cells at room temperature, and caused internalization and lysosomal degradation of the glycine receptors at 37°C. Immunoglobulin G antibodies bound to rodent spinal cord and brainstem co-localizing with monoclonal antibodies to glycine receptor-α1. Ten glycine receptor antibody positive samples were also identified in a retrospective cohort of 56 patients with stiff person syndrome and related syndromes. Glycine receptor antibodies are strongly associated with spinal and brainstem disorders, and the majority of patients have progressive encephalomyelitis with rigidity and myoclonus. The antibodies demonstrate in vitro evidence of pathogenicity and the patients respond well to immunotherapies, contrasting with earlier studies of this syndrome, which indicated a poor prognosis. The presence of glycine receptor antibodies should help to identify a disease that responds to immunotherapies, but these treatments may need to be sustained, relapses can occur and maintenance immunosuppression may be required.
Asunto(s)
Anticuerpos/sangre , Encefalomielitis/inmunología , Rigidez Muscular/inmunología , Mioclonía/inmunología , Receptores de Glicina/inmunología , Síndrome de la Persona Rígida/inmunología , Adolescente , Adulto , Anciano , Animales , Anticuerpos/líquido cefalorraquídeo , Niño , Preescolar , Comorbilidad , Encefalomielitis/tratamiento farmacológico , Encefalomielitis/epidemiología , Encefalomielitis/fisiopatología , Epilepsias Mioclónicas/epidemiología , Femenino , Glutamato Descarboxilasa/inmunología , Células HEK293 , Humanos , Lactante , Masculino , Persona de Mediana Edad , Rigidez Muscular/tratamiento farmacológico , Rigidez Muscular/epidemiología , Rigidez Muscular/fisiopatología , Mioclonía/tratamiento farmacológico , Mioclonía/epidemiología , Mioclonía/fisiopatología , Neoplasias/epidemiología , Evaluación de Resultado en la Atención de Salud , Canales de Potasio con Entrada de Voltaje/inmunología , Estudios Prospectivos , Ratas , Síndrome de la Persona Rígida/tratamiento farmacológico , Síndrome de la Persona Rígida/epidemiología , Síndrome de la Persona Rígida/fisiopatología , Síndrome , Adulto JovenRESUMEN
Stiff man syndrome (SMS) and its variants are rare neurological disorders with unusual, often awkward motor and psychological symptoms. Misdiagnoses are frequent and differentiation from psychogenic movement disorder may be difficult. Clinical suspicion can be substantiated by neurophysiological and immunological testing. Autoimmunity against certain proteins of inhibitory synapses appears to be a key feature that links SMS to other autoimmune encephalopathies and endocrinopathies. According to retrospective analyses a front-loaded long-term methylprednisolone treatment appears to be most effective.
Asunto(s)
Autoanticuerpos/inmunología , Errores Diagnósticos/prevención & control , Metilprednisolona/uso terapéutico , Síndrome de la Persona Rígida/diagnóstico , Síndrome de la Persona Rígida/inmunología , Antiinflamatorios/uso terapéutico , Diagnóstico Diferencial , Humanos , Fármacos Neuroprotectores/uso terapéutico , Síndrome de la Persona Rígida/tratamiento farmacológicoRESUMEN
Stiff-Man syndrome (SMS) is a rare disease of the central nervous system (CNS) characterized by progressive rigidity of the body musculature with superimposed painful spasms. An autoimmune origin of the disease has been proposed. In a caseload of more than 100 SMS patients, 60% were found positive for autoantibodies directed against the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD). Few patients, all women affected by breast cancer, were negative for GAD autoantibodies but positive for autoantibodies directed against a 128-kD synaptic protein. We report here that this antigen is amphiphysin. GAD and amphiphysin are nonintrinsic membrane proteins that are concentrated in nerve terminals, where a pool of both proteins is associated with the cytoplasmic surface of synaptic vesicles. GAD and amphiphysin are the only two known targets of CNS autoimmunity with this distribution. This finding suggests a possible link between autoimmunity directed against cytoplasmic proteins associated with synaptic vesicles and SMS.
Asunto(s)
Autoantígenos/química , Neoplasias de la Mama/inmunología , Proteínas del Tejido Nervioso/inmunología , Síndrome de la Persona Rígida/inmunología , Enfermedades Autoinmunes/inmunología , Western Blotting , Femenino , Humanos , Peso Molecular , Proteínas del Tejido Nervioso/química , Distribución TisularRESUMEN
A 34-year-old woman developed walking disability with wheelchair dependency for more than 2 years due to chronic regional pain syndrome type II (CRPS II) in the feet. After excluding neurological and vascular disease, lumbar sympathectomy was performed on both sides. Surgical treatment was uneventful, and the patient's symptoms dramatically improved after 2 months. She is now able to walk some 500 m. This case illustrates the fact that surgical lumbar sympathectomy is an effective alternative or adjunct treatment even in fixed CRPS II.
Asunto(s)
Síndromes de Dolor Regional Complejo/rehabilitación , Plexo Lumbosacro/cirugía , Síndromes de Dolor Regional Complejo/cirugía , Simpatectomía , Caminata , Silla de RuedasRESUMEN
In MS patients with contraindications, intolerance, or failure of established immunomodulatory drugs, intravenous immunoglobulins (IVIG) are increasingly being administered. Several clinical studies recently showed that IVIG are generally safe, well tolerated and only occasionally have serious side effects. While some studies indicated beneficial effects from IVIG in relapsing-remitting MS, the recently published PRIVIG study failed to show any clinical benefit. Although pregnancy and the post-partum period appear to be interesting potential indications for IVIG, since under those conditions all other immunomodulatory drugs except for corticosteroids are not indicated, there are no data from adequate studies to support the use of IVIG in this patient group. For other indications in MS patients, study results are either negative or lacking. Overall IVIG may be considered a safe second-line compound in patients with relapsing-remitting MS. However, efficacy, long-term consequences, and optimal dosage of IVIG have not been unequivocally ascertained as yet.
Asunto(s)
Inmunoglobulinas/administración & dosificación , Inmunoglobulinas/efectos adversos , Esclerosis Múltiple/tratamiento farmacológico , Humanos , Factores Inmunológicos/administración & dosificación , Inyecciones Intravenosas , Resultado del TratamientoRESUMEN
Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy in humans and has been associated with a partial duplication of chromosome 17 (CMT type 1A). We have generated a transgenic rat model of this disease and provide experimental evidence that CMT1A is caused by increased expression of the gene for peripheral myelin protein-22 (PMP22, gas-3). PMP22-transgenic rats develop gait abnormalities caused by a peripheral hypomyelination, Schwann cell hypertrophy (onion bulb formation), and muscle weakness. Reduced nerve conduction velocities closely resemble recordings in human patients with CMT1A. When bred to homozygosity, transgenic animals completely fail to elaborate myelin. We anticipate that the CMT rat model will facilitate the identification of a cellular disease mechanism and serve in the evaluation of potential treatment strategies.
Asunto(s)
Enfermedad de Charcot-Marie-Tooth/genética , Proteínas de la Mielina/genética , Animales , Animales Modificados Genéticamente , Secuencia de Bases , Cartilla de ADN/química , Enfermedades Desmielinizantes/genética , Modelos Animales de Enfermedad , Expresión Génica , Homocigoto , Humanos , Datos de Secuencia Molecular , Conducción Nerviosa , Ratas , Células de Schwann/citologíaRESUMEN
Exaggerated startle is an uncommon feature of various neurological diseases, but is still lacking precise analysis in many of them. So far, electrophysiologic and cinematographic analyses allow discriminating two main subtypes. The prototype of primary exaggerated startle is hereditary hyperekplexia, a well-studied disorder of the inhibitory glycine receptor and thus of the neuronal Cl- channel. The involuntary jerking in hereditary hyperekplexia is considered a reticular reflex myoclonus. The prototype of primary normal startle with secondary abnormalities is startle epilepsy where a surprise stimulus typically provokes a normal startle, which in turn initiates a focal (most often frontal lobe) seizure with tonic posturing of the limbs. Clinical differential diagnosis between both subtypes may be difficult in individual cases, but there are abnormalities in clinical and neurophysiologic reflex testing, which need, however, broad validation.
Asunto(s)
Epilepsias Mioclónicas/fisiopatología , Mioclonía/fisiopatología , Reflejo Anormal , Reflejo de Sobresalto/fisiología , Formación Reticular/fisiopatología , Adulto , Tronco Encefálico/fisiopatología , Niño , Canales de Cloruro/química , Canales de Cloruro/genética , Canales de Cloruro/fisiología , Cultura , Diagnóstico Diferencial , Humanos , Recién Nacido , Trastornos Mentales/etiología , Mioclonía/psicología , Receptores de Glicina/química , Receptores de Glicina/genética , Receptores de Glicina/fisiología , Convulsiones/fisiopatología , Médula Espinal/fisiopatología , Relación Estructura-ActividadRESUMEN
OBJECTIVE: The objective of this study was to evaluate the clinical usefulness of whole-body magnetic resonance imaging (MRI) in facio-scapulo-humeral muscular dystrophy (FSHD). METHODS: In 20 patients with genetically proven FSHD1, we prospectively assessed muscular involvement and correlated the results of semi-quantitative manual muscle testing and other parameters such as disease duration, creatine kinase (CK) levels and repeat length of the D4Z4 locus with whole-body MRI. RESULTS: Clinical muscle testing revealed the trapezius, pectoralis and infraspinatus as the most severely affected muscles in the shoulder, and the knee flexors and gluteus medius in the hip girdle. MRI revealed the trapezius and serratus anterior muscles in the shoulder, and the hamstrings and adductor muscles in the hip girdle, as the most severely affected muscle groups. Overall, degrees of fatty degeneration on MRI scans correlated significantly with clinical weakness. Moreover, we could detect clear affection of the trunk muscles. Corresponding to earlier reports, asymmetric involvement was frequent in both clinical examination and MRI scoring. Moreover, MRI revealed inhomogeneous muscle degeneration in a considerable proportion of both, muscles and patients. Both clinical and MRI scores significantly correlated to disease duration, but not to fragment size or CK levels. CONCLUSION: Fatty degeneration in whole-body MRI correlates well to clinical muscle testing of the extremities but gives more information on deeper or trunk muscles. It shows structural changes in muscular disorders and may become an excellent tool for assessment of muscle involvement and follow-up studies.
Asunto(s)
Imagen por Resonancia Magnética/métodos , Músculo Esquelético/diagnóstico por imagen , Distrofia Muscular Facioescapulohumeral/diagnóstico , Distrofia Muscular Facioescapulohumeral/patología , Examen Físico/métodos , Imagen de Cuerpo Entero/métodos , Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Aumento de la Imagen/métodos , Interpretación de Imagen Asistida por Computador/métodos , Masculino , Persona de Mediana Edad , Fuerza Muscular , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Cytoplasmic islet cell antibodies are well-established predictive markers of IDDM. Although target molecules of ICA have been suggested to be gangliosides, human monoclonal ICA of the immunoglobulin G class (MICA 1-6) produced from a patient with newly diagnosed IDDM recognized glutamate decarboxylase as a target antigen. Here we analyzed the possible heterogeneity of target antigens of ICA by subtracting the GAD-specific ICA staining from total ICA staining of sera. This was achieved 1) by preabsorption of ICA+ sera with recombinant GAD65 and/or GAD67 expressed in a baculovirus system and 2) by ICA analysis of sera on mouse pancreas, as GAD antibodies do not stain mouse islets in the immunofluorescence test. We show that 24 of 25 sera from newly diagnosed patients with IDDM recognize islet antigens besides GAD. In contrast, GAD was the only islet antigen recognized by ICA from 7 sera from patients with stiff man syndrome. Two of these sera, however, recognized antigens besides GAD in Purkinje cells. In patients with IDDM, non-GAD ICA were diverse. One group, found in 64% of the sera, stained human and mouse islets, whereas the other group of non-GAD ICA was human specific. Therefore, mouse islets distinguish two groups of non-GAD ICA and lack additional target epitopes of ICA besides GAD. Longitudinal analysis of 6 sera from nondiabetic ICA+ individuals revealed that mouse-reactive ICA may appear closer to clinical onset of IDDM in some individuals. Mouse-reactive ICAs, however, remained absent in 36% of the patients at diagnosis of IDDM.
Asunto(s)
Antígenos/inmunología , Autoanticuerpos/inmunología , Diabetes Mellitus Tipo 1/inmunología , Islotes Pancreáticos/inmunología , Síndrome de la Persona Rígida/inmunología , Adolescente , Adulto , Anciano , Animales , Anticuerpos/inmunología , Especificidad de Anticuerpos , Autoanticuerpos/sangre , Encéfalo/inmunología , Niño , Diabetes Mellitus Tipo 1/epidemiología , Técnica del Anticuerpo Fluorescente , Glutamato Descarboxilasa/inmunología , Glutamato Descarboxilasa/farmacología , Humanos , Isomerismo , Estudios Longitudinales , Ratones , Ratones Endogámicos BALB C , Persona de Mediana Edad , Células de Purkinje/inmunología , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/farmacología , Especificidad de la EspecieRESUMEN
OBJECTIVE: To describe mental retardation and microcephaly as initial clinical signs in myotonic dystrophy (MD) with high trinucleotide repeats. PATIENTS AND METHODS: Two patients with maternally inherited MD were examined. Southern blot analysis was performed and trinucleotide repeat expansions were related to the findings of clinical and magnetic resonance imaging investigations. RESULTS: Both patients had the large CTG trinucleotide repeat expansions often seen in congenital MD, but they lacked the typical clinical signs. Mental retardation and microcephaly were the leading features present in infancy. Muscular weakness, in contrast, developed after age 35 years. Although there was no evidence for perinatal asphyxia or sleep apnea, magnetic resonance imaging disclosed reduced brain volume and subcortical demyelination. CONCLUSIONS: Mental retardation preceding the development of muscle weakness suggests that the cerebral involvement in MD is a direct consequence of the genetic disorder and not mediated by muscle disease. Careful clinical examination of the parents for signs of MD should be considered in patients with cognitive deficits even without apparent muscular involvement.
Asunto(s)
Discapacidad Intelectual/genética , Distrofia Miotónica/genética , Repeticiones de Trinucleótidos , Adulto , Femenino , Humanos , Persona de Mediana EdadRESUMEN
We report a 70-year-old patient who presented with a 4-year history of weakness of paravertebral muscles. Electrodiagnostic studies revealed a mixed neurogenic-myopathic pattern. Light microscopic examination revealed atrophic fibers with rimmed vacuoles; electron microscopy demonstrated cytoplasmic and intranuclear filaments measuring about 16 nm in width, consistent with the diagnosis of inclusion body myositis. Therapy with corticosteroids provided only a mild and transient benefit. Ten months after the initial evaluation, clinical and electrodiagnostic examination demonstrated mild progression of the disease.
Asunto(s)
Cuerpos de Inclusión , Miositis/patología , Paresia/patología , Anciano , Humanos , Masculino , Músculos/ultraestructura , Columna VertebralRESUMEN
Retrospective psychological evaluation of nine patients with stiff-man syndrome (SMS), seven of whom evidenced autoimmune disease, revealed a characteristic set of psychological symptoms or features: Major stressful life events preceded the development of permanent symptoms by 6 months or less (seven patients); transient motor symptoms occurred in emotionally distressing situations months or even years before the onset of a permanent motor deficit (five patients); after onset, similar situations specifically precipitated or augmented stiffness and spasms (five patients). We also found task-specific fear resembling agoraphobia (six patients) and loss or invalidation of one or both parents, or loss of home, in childhood (seven patients). Eight patients were initially misdiagnosed as having psychogenic movement disorder. We conclude that the common misdiagnosis of SMS as a psychogenic movement disorder is due to the compelling association of a set of salient psychological features, bizarre and fluctuating motor symptoms, and lack of approved neurologic signs.
Asunto(s)
Síndrome de la Persona Rígida/psicología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración PsiquiátricaRESUMEN
We report a patient who developed stiff-man syndrome, including disabling shoulder subluxation and wrist ankylosis, in association with breast cancer. Immunologic investigations disclosed autoimmunity directed against not only glutamic acid decarboxylase but also amphiphysin, a 128-kd protein located in the presynaptic compartment of neurons. The patient improved after surgery and corticosteroid treatment and has been stable for nearly 4 years on only anti-estrogenics. The triad of stiff-man syndrome, breast cancer, and autoantibodies against amphiphysin identifies a new autoimmune paraneoplastic syndrome of the CNS.
Asunto(s)
Neoplasias de la Mama/complicaciones , Carcinoma Ductal de Mama/complicaciones , Síndromes Paraneoplásicos/complicaciones , Síndrome de la Persona Rígida/etiología , Animales , Autoanticuerpos/sangre , Autoanticuerpos/aislamiento & purificación , Western Blotting , Diagnóstico Diferencial , Femenino , Glutamato Descarboxilasa/inmunología , Humanos , Técnicas para Inmunoenzimas , Persona de Mediana Edad , Proteínas del Tejido Nervioso/inmunología , Síndromes Paraneoplásicos/inmunología , Pruebas de Precipitina , Ratas , Síndrome de la Persona Rígida/diagnóstico , Síndrome de la Persona Rígida/inmunologíaRESUMEN
MRI and CSF investigations revealed meningeal involvement in a 29-year-old patient with biopsy-confirmed Wegener's granulomatosis. The intracranial manifestation of Wegener's granulomatosis was supported by the detection of pathologic circulating antineutrophil cytoplasm (c-ANCA) in the CSF. We monitored disease activity by c-ANCA measurement in the CSF. After repeated cycles of intrathecal administration of methotrexate and corticoids, progression of meningeal infiltration stopped, and CSF c-ANCA titers became negative.
Asunto(s)
Anticuerpos Anticitoplasma de Neutrófilos/líquido cefalorraquídeo , Granulomatosis con Poliangitis/líquido cefalorraquídeo , Granulomatosis con Poliangitis/patología , Meninges/patología , Adulto , Anticuerpos/análisis , Dexametasona/uso terapéutico , Quimioterapia Combinada , Granulomatosis con Poliangitis/inmunología , Humanos , Imagen por Resonancia Magnética , Masculino , Metotrexato/uso terapéutico , Metilprednisolona/uso terapéutico , Mieloblastina , Serina Endopeptidasas/inmunologíaRESUMEN
We report on eight patients with stiff-man syndrome (SMS) or its "plus" variant, progressive encephalomyelopathy with rigidity and myoclonus (PERM) receiving intrathecal baclofen via pump. In six of the patients, follow-ups continued for approximately 2.5 to 6.5 years after pump implantation. Intrathecal baclofen was an effective last-resort alternative for patients who responded poorly to or did not tolerate oral antispasticity medications. General mobility increased, and spasms and rigidity were reduced; however, no complete remissions were observed either before or after pump implantation. PERM patients showed more severe and rapid progression of symptoms and more attacks of autonomic dysregulation than SMS patients. They also required higher doses and more rapid dosage increases. Complications of intrathecal baclofen therapy included spasm-induced rupture of the catheter, catheter dislocation causing radicular symptoms, and pump malfunction resulting in inaccurate dosage administration. Patients suffered fewer side effects with intrathecal baclofen than with oral medication, but overdose resulted in a transient, comalike state in one patient and sudden dosage reduction due to pump failure was fatal in another.
Asunto(s)
Baclofeno/uso terapéutico , Enfermedades del Sistema Nervioso Central/complicaciones , Enfermedades del Sistema Nervioso Central/tratamiento farmacológico , Relajantes Musculares Centrales/uso terapéutico , Rigidez Muscular/complicaciones , Mioclonía/complicaciones , Síndrome de la Persona Rígida/tratamiento farmacológico , Adulto , Anciano , Baclofeno/efectos adversos , Enfermedades del Sistema Nervioso Central/fisiopatología , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Humanos , Inyecciones Espinales , Masculino , Persona de Mediana Edad , Relajantes Musculares Centrales/efectos adversos , Resultado del TratamientoRESUMEN
Proximal myotonic myopathy (PROMM) is an autosomal dominantly inherited multisystemic disorder characterized by myotonia, proximal muscle weakness, and cataracts. This disorder is not linked to the gene locus of myotonic dystrophy (DM). We describe three new families with PROMM. In all patients, CTG repeats of the DM gene in DNA from blood leukocytes were normal. MRI of the brain revealed a consistent pattern of marked white matter hyperintensity on T2-weighted images in four patients; two additional patients had similar but mild to moderate MRI abnormalities. The morphology of these abnormalities is unknown. Clinical symptoms of brain disease were not consistent and included mental changes with hypersomnia, parkinsonian features, stroke-like episodes, and seizures. The causative relationship of these clinical features with the MRI white matter abnormalities remains to be established. Our observations suggest that PROMM may involve the brain.
Asunto(s)
Encéfalo/patología , Imagen por Resonancia Magnética , Miotonía/diagnóstico , Adulto , Trastornos Cerebrovasculares/complicaciones , ADN/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Músculos/patología , Miotonía/genética , Miotonía/fisiopatología , Linaje , Fases del SueñoRESUMEN
We report on 2 sisters with an autosomal-recessive multiple pterygium syndrome, type Escobar, consisting of multiple pterygia with severe contractures, short stature, and minor facial and external genital anomalies. The striking finding was severe muscular atrophy. We speculate that a neuromuscular disorder is the underlying pathogenesis of Escobar syndrome.
Asunto(s)
Anomalías Múltiples/fisiopatología , Anomalías Múltiples/genética , Artrogriposis/fisiopatología , Estatura , Niño , Cara/anomalías , Femenino , Genitales Femeninos/anomalías , Deformidades Congénitas de la Mano/fisiopatología , Humanos , Recién Nacido , SíndromeRESUMEN
Antibodies to the 40 kD antigen (identified as tyrosine phosphatase IA-2) and glutamate decarboxylase (GAD65) are strongly associated with insulin dependent diabetes mellitus (IDDM). However, antibodies to GAD (GADA) can appear in the absence of IDDM, particularly in stiff man syndrome (SMS) and in some individuals with autoimmune polyendocrine syndrome type II (APS II) and organ specific autoimmune diseases. The aim of this study was to compare the specificity of IA-2 antibodies (IA-2A) and GADA for IDDM by determining their frequency in different patient groups. IA-2A were present in 64/114 (56%) IDDM patients and 9/19 (47%) APS II patients with IDDM but in only 4/28 (14%) SMS patients. 1/24 (4%) APS II patients without IDDM and 1/113 (0.9%) patients with organ specific autoimmune disease had low level IA-2A. In contrast GADA were present in 77/114 (68%) IDDM patients and 17/19 (89%) APS II patients with IDDM, but also in 25/28 (89%) SMS patients, 5/24 (21%) APS II patients without IDDM and 22/113 (19%) patients with organ specific autoimmune diseases. Furthermore, within the group of new onset IDDM, IA-2A seemed to be associated with ICA and age: 63% of ICA positive IDDM patients had IA-2A (74% had GADA) increasing to 77% in the group below 20 years of age (69% for GADA). Our results demonstrate that IA-2A may be more specific for IDDM than GADA, as the latter are also present in patients with SMS, APS II without IDDM and organ specific autoimmune diseases. IA-2A were less frequent in older patients with IDDM than GADA or ICA. A combination of IA-2A and GADA detected 84% of total and 93% of ICA positive IDDM patients.