Orthostatic myoclonus: an underrecognized cause of unsteadiness?

BACKGROUND AND PURPOSE: Recently, orthostatic myoclonus (OM) has been suggested as a cause of gait impairment and unsteadiness in neurodegenerative diseases. The aim of this study was to investigate the frequency of orthostatic myoclonus, its clinical characteristics and the underlying associated neurological disorders. METHODS: A retrospective analysis of clinical data and electromyogram surface recordings from subjects with unexplained unsteadiness/gait impairment was performed. Diagnosis of OM was made when a pattern of non-rhythmic bursts was observed (duration range 20-100 ms; bursts per second ≤16). RESULTS: Among 93 subjects studied, OM was the most frequent disorder (n = 16; 17.2%), followed by orthostatic tremor (13.9%) and low frequency tremors during orthostatism (12.9%). All patients with OM complained about unsteadiness during orthostatism and/or during gait. Leg jerking was only observed by visual inspection during orthostatism in four subjects and two also presented falls. Eleven out of 16 patients (68.7%) with OM had an associated neurodegenerative disease, such as multiple system atrophy (n = 3) Parkinson's disease (n = 2), Alzheimer's disease (n = 2), mild cognitive impairment (n = 2) and normal pressure hydrocephalus (n = 2). Although four subjects showed improvement of orthostatic myoclonus with antimyoclonic treatment, the follow-up was not systematic enough to evaluate their therapeutic effect on OM. CONCLUSIONS: Orthostatic myoclonus is often underdiagnosed and can be considered a possible cause of unsteadiness in subjects with neurodegenerative diseases. Electromyography surface recording is thereby an aid for investigating unsteadiness of unknown origin.

Temblor ortostático como causa de inestabilidad / Orthostatic tremor inducing instability

El temblor ortostático (TO) es una enfermedad neurológica de origen desconocido caracterizada por un temblor de 10-20Hz en las piernas en bipedestación. Se manifiesta por mareo e inestabilidad, que típicamente mejoran al apoyarse o sentarse y la ingesta de pequeñas cantidades de alcohol lo reduce de manera significativa. Se muestran 4 casos clínicos atendidos en nuestra consulta cuyo diagnóstico sugiere ser el de TO. Consideramos que ante un paciente con inestabilidad, es preciso plantearse como diagnóstico diferencial un TO. La historia clínica nos orienta hacia esta entidad y en caso de sospecha, el diagnóstico definitivo viene dado por el registro de la electromiografía en las extremidades inferiores en condición de reposo sentado y en ortostatismo donde se registra un temblor de 10-20Hz. El tratamiento es médico y, se emplea el clonazepam como primera opción terapéutica(AU)

Orthostatic tremor (OT) is a neurological disease of unknown aetiology. It is defined by the presence of a 10-20Hz tremor in the legs while standing still. Symptoms described are dizziness and instability that diminish if the patient sits down or leans on something; drinking small amounts of alcohol significantly reduces OT. Due to the dizziness and/or unsteadiness, these patients are usually referred to the neuro-otology department. We report 4 cases diagnosed with OT. The diagnosis of OT should be considered for patients with instability. The clinical history is a key factor to suspect this entity, and the diagnosis is given by the register of 10-20Hz contractions on limb electromyography. Treatment for this disease consists of medical treatment; the first option is clonazepam(AU)

[Orthostatic tremor inducing instability]. / Temblor ortostático como causa de inestabilidad.

Orthostatic tremor (OT) is a neurological disease of unknown aetiology. It is defined by the presence of a 10-20 Hz tremor in the legs while standing still. Symptoms described are dizziness and instability that diminish if the patient sits down or leans on something; drinking small amounts of alcohol significantly reduces OT. Due to the dizziness and/or unsteadiness, these patients are usually referred to the neuro-otology department. We report 4 cases diagnosed with OT. The diagnosis of OT should be considered for patients with instability. The clinical history is a key factor to suspect this entity, and the diagnosis is given by the register of 10-20 Hz contractions on limb electromyography. Treatment for this disease consists of medical treatment; the first option is clonazepam.

Computational classifiers for predicting the short-term course of Multiple sclerosis.

BACKGROUND: The aim of this study was to assess the diagnostic accuracy (sensitivity and specificity) of clinical, imaging and motor evoked potentials (MEP) for predicting the short-term prognosis of multiple sclerosis (MS). METHODS: We obtained clinical data, MRI and MEP from a prospective cohort of 51 patients and 20 matched controls followed for two years. Clinical end-points recorded were: 1) expanded disability status scale (EDSS), 2) disability progression, and 3) new relapses. We constructed computational classifiers (Bayesian, random decision-trees, simple logistic-linear regression-and neural networks) and calculated their accuracy by means of a 10-fold cross-validation method. We also validated our findings with a second cohort of 96 MS patients from a second center. RESULTS: We found that disability at baseline, grey matter volume and MEP were the variables that better correlated with clinical end-points, although their diagnostic accuracy was low. However, classifiers combining the most informative variables, namely baseline disability (EDSS), MRI lesion load and central motor conduction time (CMCT), were much more accurate in predicting future disability. Using the most informative variables (especially EDSS and CMCT) we developed a neural network (NNet) that attained a good performance for predicting the EDSS change. The predictive ability of the neural network was validated in an independent cohort obtaining similar accuracy (80%) for predicting the change in the EDSS two years later. CONCLUSIONS: The usefulness of clinical variables for predicting the course of MS on an individual basis is limited, despite being associated with the disease course. By training a NNet with the most informative variables we achieved a good accuracy for predicting short-term disability.

Isolated dysphagia due to paraneoplastic myasthenic syndrome with anti-P/Q-type voltage-gated calcium-channel and anti-acetylcholine receptor antibodies.

Dysphagia is a common symptom in neuromuscular junction disorders, but it rarely occurs in isolation or is the presenting feature. We describe a patient presenting with isolated dysphagia to liquids. Electrophysiological studies, such as repetitive nerve stimulation and single-fiber electromyography, were normal. Serum anti-P/Q-type voltage-gated calcium-channel (anti-P/Q-type VGCC) and anti-acetylcholine receptor (AChR ab) antibodies were above the normal range. A computed tomography scan showed a mediastinal mass corresponding to a thymic carcinoma. After chemotherapy, surgical removal of the thymic carcinoma and radiotherapy, the patient no longer complained of dysphagia, AChR ab titers were reduced and anti-P/Q-type VGCC antibodies became negative. To the best of our knowledge, no previous reports of a paraneoplastic myasthenic syndrome related to thymic carcinoma with both anti-P/Q-type VGCC and AChR antibodies have been described.

Peripheral nerve regeneration through allografts compared with autografts in FK506-treated monkeys.

OBJECT: The clinical use of nerve allografts combined with immunosuppressant therapy has become a genuine possibility that could supersede the classic use of autografts. However, contradictory data have been reported on whether immunosuppressant therapy should be temporarily administered. The purpose of this study was to compare the nerve regeneration obtained using ulnar nerve allografts in nonhuman primates temporarily treated with FK506 (tacrolimus) with that obtained using nerve autografts. METHODS: Four-centimeter nerve autografts or allografts were placed in the distal ulnar motor nerve of eight monkeys. The FK506 was temporarily administered to the animals of the allograft group for 2 months. At periods of 3, 5, and 8 months postsurgery, quantitative electrophysiological recordings were obtained to estimate muscle response. A quantitative analysis of ulnar motor neurons in the spinal cord was performed and axons were counted stereologically. No statistically significant differences were found in the neuronal and axonal counts between autograft and allograft groups at 8 months. The electrophysiological studies showed no differences relative to the amplitude, but the autograft group presented with a greater nerve conduction velocity (NCV). However, no statistically significant differences were found between the number of neurons and distal axonal counts in the two groups. CONCLUSIONS: Nerve regeneration through cold-preserved allografts in a primate model temporarily treated with FK506 was similar to that obtained using nerve autografts, in terms of neuronal and axonal counts. Nevertheless, temporary immunosuppression produced lower NCV when allografts were used, with less maturation of the myelinated fibers, which indicated that a partial rejection had taken place.

Nerve regeneration through nerve autografts and cold preserved allografts using tacrolimus (FK506) in a facial paralysis model: a topographical and neurophysiological study in monkeys.

OBJECTIVE: Nerve regeneration through cold preserved nerve allografts is demonstrated, and treatment of nerve allografts with FK506 induces better regeneration than other immunosuppressants. We study nerve regeneration through cold preserved nerve allografts temporarily treated with FK506 and compare it with the regeneration obtained using classic nerve autografts in a facial paralysis model in monkeys. METHODS: A trunk of the facial nerve on both sides was transected in eight monkeys and immediately repaired with a 3 to 4 cm nerve autograft or allograft. FK506 was administered to the animals of the allograft group for 2 months, and nerve allografts were cold preserved for 3 weeks. At periods of 3, 5, and 8 months after surgery, quantitative electrophysiological assessment and video recordings were performed. At the end of the study, quantitative analysis of neurons in the facial nucleus was carried out, and axons were stereologically counted. RESULTS: After the regenerative period, neuronal density was higher in the autograft group. However, distal axonal counts were similar in both groups. Serial electrophysiological recordings and histology of nerve allografts showed that the grafts were partially rejected after cessation of the immunosuppressant. CONCLUSION: The regeneration through nerve allografts temporarily treated with FK506 does not achieve the electrophysiological results and neuronal counts achieved with nerve autografts, but axonal collateralization in the allografts induces a similar activation of mimic muscles.