Clinical guide for the diagnosis and follow-up of myotonic dystrophy type 1, MD1 or Steinert's disease. / Guía clínica para el diagnóstico y seguimiento de la distrofia miotónica tipo 1, DM1 o enfermedad de Steinert.

BACKGROUND AND OBJECTIVES: Steinert's disease or myotonic dystrophy type 1 (MD1), (OMIM 160900), is the most prevalent myopathy in adults. It is a multisystemic disorder with dysfunction of virtually all organs and tissues and a great phenotypical variability, which implies that it has to be addressed by different specialities with experience in the disease. The knowledge of the disease and its management has changed dramatically in recent years. This guide tries to establish recommendations for the diagnosis, prognosis, follow-up and treatment of the complications of MD1. MATERIAL AND METHODS: Consensus guide developed through a multidisciplinary approach with a systematic literature review. Neurologists, pulmonologists, cardiologists, endocrinologists, neuropaediatricians and geneticists have participated in the guide. RECOMMENDATIONS: The genetic diagnosis should quantify the number of CTG repetitions. MD1 patients need cardiac and respiratory lifetime follow-up. Before any surgery under general anaesthesia, a respiratory evaluation must be done. Dysphagia must be screened periodically. Genetic counselling must be offered to patients and relatives. CONCLUSION: MD1 is a multisystemic disease that requires specialised multidisciplinary follow-up.

¿Rombencefalomielitis aguda recurrente del adulto o neuromielitis óptica? A propósito de un caso / Recurrent acute rhombencephalomyelitis in an adult or neuromyelitis optica? Presentation of a case

Introducción: La falta de criterios homogéneos aceptados para la definición de algunas de las patologías desmielinizantes dificulta la caracterización diagnóstica limitando la reproducibilidad de los resultados y las recomendaciones terapéuticas. Especialmente controvertidas son las formas de encefalomielitis recurrentes (EAD-RR) y otras formas infrecuentes de neuromielitis óptica (NMO).Objetivo: Describimos la evolución clínico-radiológica de un caso de EAD-RR del adulto versus NMO, seguida durante 9 años. Paciente y métodos: La paciente debutó con síntomas severos de rombencefalomielitis y la resonancia magnética (RM) craneal y medular mostraron lesiones extensas, con captación de gadolinio en el tronco encefálico y de la médula, acorde con los síntomas clínicos de la paciente. Se excluyó etiología infecciosa, el índice IgG fue normal y fueron negativos los anticuerpos para NMO. Tras tratamiento con corticoides por vía intravenosa y plasmaféresis la recuperación del episodio fue excelente. Durante el seguimiento ha presentado 7 recurrencias, preferentemente medulares, con buena recuperación, que reproducen con severidad variable los mismos síntomas. Desde el inicio ha recibido tratamiento inmunosupresor. Conclusiones: Nuestro caso comparte características clínicas con EAD-RR y NMO e ilustra que, pese a los criterios vigentes, la caracterización diagnóstica de estas entidades no es fácil (AU)

Introduction: The lack of accepted homogeneous criteria for the definition of some demyelinating diseases makes diagnostic characterization difficult and limits data interpretation and therapeutic recommendations. Recurrent encephalomyelitis (ADE-R) along with borderline cases of neuromyelitis optica (NMO) are especially controversial. Objective:To describe the clinical and radiological evolution of an adult-onset ADE-R versus NMO case throughout 9 years of follow-up. Patient and methods: Our patient presented with severe symptoms of rhombencephalomyelitis and the cranial and spinal magnetic resonance imaging (MRI) showed large lesions, with gadolinium enhancement in brainstem and spinal cord, correlating with the clinical picture. Infectious aetiology was excluded, IgG index was normal and NMO antibodies were negative. After treatment with intravenous corticosteroids and plasmapheresis, there was excellent recovery in the acute phase. During follow-up, seven relapses have occurred, mainly in the spinal cord, with good recovery and the same symptomatology, albeit with different severity. Immunosuppressive treatment was introduced since the beginning.Conclusions: Our case shares common features of both ADE-R and NMO, illustrating that diagnostic characterization is not easy in spite of current criteria (AU)

Long-lasting treatment effect of rituximab in MuSK myasthenia.

OBJECTIVE: Rituximab has emerged as an efficacious option for drug-resistant myasthenia gravis (MG). However, reports published only describe the short-term follow-up of patients treated and little is known about their long-term clinical and immunologic evolution. Our objective was to report the clinical and immunologic long-term follow-up of 17 patients (6 MuSK+MG and 11 AChR+MG) and compare the response between AChR+MG and MuSK+MG patients. METHODS: Myasthenia Gravis Foundation America postintervention status and changes in treatment and antibody titers were periodically determined. Lymphocyte subpopulations, total immunoglobulin, immunoglobulin G (IgG) anti-MuSK subclasses, and anti-tetanus toxoid IgG before and after treatment were also studied. RESULTS: After a mean post-treatment period of 31 months, 10 of the AChR+MG patients improved but 6 of them needed reinfusions. In contrast, all MuSK+MG patients achieved a remission (4/6) or minimal manifestations (2/6) status and no reinfusions were needed. Consequently, in the MuSK+MG group, prednisone doses were significantly reduced and concomitant immunosuppressants could be withdrawn. Clinical improvement was associated with a significant decrease in the antibody titers only in the 6 MuSK+MG patients. At last follow-up MuSK antibodies were negative in 3 of these patients and showed a decrease of over 80% in the other 3. CONCLUSION: In view of the long-lasting benefit observed in MuSK+MG patients, we recommend to use rituximab as an early therapeutic option in this group of patients with MG if they do not respond to prednisone. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that IV rituximab improves the clinical and immunologic status of patients with MuSK+MG.

[Recurrent acute rhombencephalomyelitis in an adult or neuromyelitis optica? Presentation of a case]. / ¿Rombencefalomielitis aguda recurrente del adulto o neuromielitis óptica? A propósito de un caso.

INTRODUCTION: The lack of accepted homogeneous criteria for the definition of some demyelinating diseases makes diagnostic characterization difficult and limits data interpretation and therapeutic recommendations. Recurrent encephalomyelitis (ADE-R) along with borderline cases of neuromyelitis optica (NMO) are especially controversial. OBJECTIVE: To describe the clinical and radiological evolution of an adult-onset ADE-R versus NMO case throughout 9 years of follow-up. PATIENT AND METHODS: Our patient presented with severe symptoms of rhombencephalomyelitis and the cranial and spinal magnetic resonance imaging (MRI) showed large lesions, with gadolinium enhancement in brainstem and spinal cord, correlating with the clinical picture. Infectious aetiology was excluded, IgG index was normal and NMO antibodies were negative. After treatment with intravenous corticosteroids and plasmapheresis, there was excellent recovery in the acute phase. During follow-up, seven relapses have occurred, mainly in the spinal cord, with good recovery and the same symptomatology, albeit with different severity. Immunosuppressive treatment was introduced since the beginning. CONCLUSIONS: Our case shares common features of both ADE-R and NMO, illustrating that diagnostic characterization is not easy in spite of current criteria.

[Catastrophic neuromuscular diseases]. / Enfermedades neuromusculares catastrófi cas.

Neurologists should anticipate and recognize the onset of respiratory failure in patients with neuromuscular diseases. Symptoms vary according to the speed of onset of respiratory muscle weakness. Catastrophic situations usually occur in three clinical scenarios: 1) incorrect management of acute respiratory failure of neuromuscular origin, autonomic dysfunction or during general anaesthesia of patients with neuromuscular diseases ; 2) incorrect prognosis and treatment due to the lack of a correct diagnosis. This situation is more common in ventilated patients with associated muscular weakness, acute neuropathies or motor neuron disease, and 3) inappropriate medical intervention in patients with neuromuscular disease with a definitive diagnosis but longstanding disease (amyotrophic lateral sclerosis, spinal muscular atrophy, myotonic dystrophy and other muscular dystrophies).

Enfermedades neuromusculares catastróficas / Catastrophic neuromuscular diseases

El neurólogo debe anticipar y reconocer el inicio de la insuficiencia respiratoria en los pacientes neuromusculares. La sintomatología varía en función de la velocidad de instauración de la debilidad de la musculatura respiratoria. Las situaciones de catástrofe sue- len acontecer en 3 supuestos clínicos: 1) manejo incorrecto de una insuficiencia respiratoria aguda de origen neuromuscular, disautonomía o durante una anestesia general a pacientes neuromusculares; 2) pronóstico y tratamiento erróneos por falta de un diagnóstico acertado; esta situación es más frecuente en pacientes críticos dependientes de un ventilador con debilidad muscular asociada, en el diferencial de neuropatías agudas o enfermedad de la neurona motora, y 3) inadecuada actuación médica en el paciente neuromuscular con diagnóstico definido, pero con larga evolución (esclerosis lateral amiotrófica, atrofia muscular espinal, distrofia miotónica y otras distrofias musculares) (AU)

Neurologists should anticipate and recognize the onset of respiratory failure in patients with neuromuscular diseases. Symptoms vary according to the speed of onset of respiratory muscle weakness. Catastrophic situations usually occur in three clinical scenarios: 1) incorrect management of acute respiratory failure of neuromuscular origin, autonomic dysfunction or during general anaesthesia of patients with neuromuscular diseases ; 2) incorrect prognosis and treatment due to the lack of a correct diagnosis. This situation is more common in ventilated patients with associated muscular weakness, acute neuropathies or motor neuron disease, and 3) inappropriate medical intervention in patients with neuromuscular disease with a definitive diagnosis but longstanding disease (amyotrophic lateral sclerosis, spinal muscular atrophy, myotonic dystrophy and other muscular dystrophies) (AU)

[Prolonged acute renal failure and severe polyradiculopathy in ethylene glycol intoxication]. / Fracaso renal agudo prolongado y polirradiculopatía severa en paciente intoxicado con etilenglicol.

Ethylene glycol intoxication involves acute renal failure and severe metabolic acidosis. Prolonged renal insufficiency can occur but terminal chronic renal failure has been reported in very few cases. We describe a patient who after ingestion of 920 ml of ethylene glycol developed prolonged acute renal failure needing hemodialysis for 37 days and then he partly recovered renal function. The patient developed a severe sensitive-motor and autonomic polyradiculopathy.

[Segmental motor paralysis caused by the varicella zoster virus. Clinical study and functional prognosis]. / Parálisis motora segmentaria por virus varicela-zoster. Estudio clínico y pronóstico funcional.

INTRODUCTION: Segmental motor paralysis of the limbs (SMP) complicates 2-3% of the cases of cutaneous herpes zoster. Viral invasion and inflammation of the motor neurons of the anterior horn cells by the varicella-zoster virus (VVZ) causes clinical weakness at the same time and site as the cutaneous eruption. OBJECTIVES: To analyze the clinical findings, complementary investigations and functional prognosis of patients with SMP at brachial plexus and lumbosacral levels. PATIENTS AND METHODS: We made a retrospective study of 10 patients with SMP admitted to the Hospital Universitario Gregorio Maranon de Madrid during 1989-1999, aged between 38 and 84 years (6 women, 4 men). Neurological examination was done, including muscle balance, complementary studies including microbiology (serum and CSF serology, viral PCR-ADN), neurophysiology using MNR of the spine and plexuses and functional prognosis on the NDS, NSS and RANKIN scales. RESULTS: There is a close relationship between dermatome and myotome involvement (90%). The brachial and lumbosacral plexuses were equally affected (50%). Plasma and CSF VVZ serology was positive in 50% of the cases, permitting diagnosis of a patient with no cutaneous lesions (zoster sine herpete). Denervation of the myotomes involved and the paraspinal muscles was shown on neurophysiological studies. In most cases there was functional improvement, with complete functional recovery in 80% of the cases after 12 months. CONCLUSIONS: VVZ should be considered amongst the aetiologies of SMP, even in the absence of cutaneous lesions (zoster sine herpete). The SMP coincides in time and place with the dermatome lesions. In most patients there is complete functional recovery within 12 months.

[Neurological complications of Mediterranean boutonneuse fever. Presentation of a case of acute encephalomeningomyelitis and review of the literature]. / Complicaciones neurológicas de la fiebre botonosa mediterránea. Presentación de un caso de encefalomeningomielitis aguda y revisión de la literatura.

Mediterranean spotted fever is an infectious disease due to Rickettsia conorii usually considered as benign; however, 10% of cases may have severe complications. We report a patient with celiac disease who developed encephalomeningomyelitis secondary to Mediterranean spotted fever. Meningoencephalitic involvement occurred during the acute phase, with myelitis appearing early during convalescence, as acute onset paraplegia involving the lumbosacral spinal cord. A magnetic resonance study showed multifocal white matter disturbances, with no lesions in the spinal cord. One month following onset, R. conorii antibodies serum level was 1/640. A cutaneous biopsy performed during the acute phase revealed endothelial hyperplasia, intraluminal thrombosis and lymphocytic perivascular infiltrate. Several immunological disturbances were found (circulating immune complexes, antinuclear antibodies, IgG paraproteinemia). The development of a systemic vasculitis is the major pathogenetic factor in the origin of systemic complications of Mediterranean spotted fever. We review the neurological syndromes reported in association with R. conorii infection. Our case is the second described as acute myelopathy complicating Mediterranean spotted fever.

[Giant cell arteritis, bilateral anterior ischemic optic neuropathy and anticardiolipin antibodies]. / Arteritis de células gigantes, neuropatía óptica isquémica anterior bilateral y anticuerpos anticardiolipina.

CLINICAL CASE: We report a case of giant cell arteritis (GCA) that developed acute bilateral amaurosis secondary to anterior ischemic optic neuropathy (AION), without other symptoms and with a normal erythrocyte sedimentation rate (ESR). Physical examination revealed painless and pulseless temporal arteries, ophthalmoscopic findings were blurring of margins, hyperaemia and elevation of both optic discs. Visual acuity was limited to hand motion perception and light-darkness discrimination. Six months before of this syndrome, the patient was diagnosed of polymyalgia rheumatica and was maintained asymptomatic with 6 mg/day of deflazacort. Temporal artery biopsy was diagnostic. An elevated IgG type anticardiolipin antibodies (ACA) rate was detected in serum. The remaining laboratory studies were normal. CONCLUSIONS: In old people with uni or bilateral acute visual loss, even with normal erythrocyte sedimentation rate and without other symptoms associated, it is necessary to have a high index of suspicion in order to detect giant cell arteritis. This can facilitate an early diagnosis and immediate initiation of treatment with high doses of corticosteroids. An elevated level of IgG type anticardiolipin antibodies may be a risk factor to thrombotic complications, as anterior ischemic optic neuropathy, in patients with giant cell arteritis.

[Lipidic myopathies]. / Miopatías lipídicas.

The lipid storage myopathies are produced by a biochemical defect that directly or indirectly interferes with the metabolism of fatty acids in the muscle fiber. The oxidation of fatty acids is performed by enzymes lying in the mitochondrial membranes and matrix. The phenotype is very similar between the different biochemical defects, presenting with two large groups: One with early-onset, metabolic crisis and multisystemic failure, and one with late-onset, predominant myopathy and myoglobinuria. The diagnosis of these disorders has advanced significatively in the last ten years, permitting their classification at molecular level according to the biochemical and genetic defect.

Neuroleptic malignant syndrome related to tetrabenazine introduction and haloperidol discontinuation in Huntington's disease.

We describe the second reported case of neuroleptic malignant syndrome (NMS) related to tetrabenazine therapy in Huntington's disease. In the previously reported case, factors capable of potentiating NMS included a high dosage of tetrabenazine exceeding the accepted therapeutic range, and co-medication with the dopamine-synthesis inhibitor alpha-methylparatyrosine, while in the present case abrupt introduction of the drug and discontinuation of concomitant neuroleptics may have contributed to this important adverse reaction. Uneventful recovery occurred in both cases without the need for drugs specifically enhancing dopaminergic transmission, while rechallenge by tetrabenazine with conventional doses and slow upward titration was not followed by recurrence of the NMS. Tetrabenazine has proved to be a safe and frequently useful drug in the long-term treatment of approximately 400 dyskinetic patients. We believe that NMS related to this drug is rare, provided that it is properly administered.

Interference of pentobarbital and thiopental with the vascular contraction and noradrenaline release in human cerebral arteries.

Thiopental and pentobarbital induced dose-dependent vasodilations in human cerebral arteries previously contracted with noradrenaline (NA), serotonin (5-HT) and KCl. Preincubation with both barbiturates decreased the contractions evoked by the three agents. Pentobarbital and thiopental reduced the Ca2+-induced contractile effects in K+-depolarized arteries and 5-HT-Ca2+ and NA-Ca2+ contractions dose-dependently. The tritium release evoked by K+ from these vessels prelabelled with [3H]NA was significantly reduced by both barbiturates at 10(-3) M and by Ca2+ removal. These results indicate that pentobarbital and thiopental essentially produce a similar interference with Ca2+ influx inhibiting the contractile responses induced by the three vasoactive agents and the exocytotic NA release evoked by K+.