Subject(s)
Neuralgia/diagnosis , Paresthesia/diagnosis , Polyneuropathies/diagnosis , Sarcoidosis/diagnosis , Adult , Biopsy , Diagnosis, Differential , Female , Humans , Neuralgia/pathology , Neurologic Examination , Paresthesia/pathology , Polyneuropathies/pathology , Sarcoidosis/pathology , Sarcoidosis, Pulmonary/diagnosis , Sarcoidosis, Pulmonary/pathology , Sural Nerve/pathologySubject(s)
Motor Neuron Disease/diagnosis , Multiple Sclerosis/complications , Multiple Sclerosis/diagnosis , Muscle Weakness/etiology , Upper Extremity/physiopathology , Adult , Brain/pathology , Diagnosis, Differential , Electrodiagnosis , Electromyography , Evoked Potentials, Somatosensory , Female , Humans , Magnetic Resonance Imaging , Multiple Sclerosis/pathology , Muscle Weakness/physiopathology , Neck , Neural Conduction , Spinal Cord/pathology , Spinal Cord/physiopathology , Upper Extremity/innervationABSTRACT
A prospective, multicenter, open-label study was conducted to determine the safety and efficacy of intramuscular (IM) interferon beta-1a (IFNbeta-1a) (Avonex) for treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Eligible patients received IM IFNbeta-1a 30 microg once weekly for 6 months. Safety and tolerability were evaluated by reporting of adverse events, measurement of vital signs, and results of blood chemistry, hematology, and urinalysis. The primary efficacy end points were changed from baseline to month 6 on a quantitative Neurologic Disability Score (NDS), a clinical grading (CG) scale, and grip strength (GS) measures. Electrophysiologic measurements were performed at baseline and month 6. A total of 20 treatment-resistant patients with CIDP were enrolled in the study. The tolerability of IFNbeta-1a in patients with CIDP was similar to that seen with its use in MS. There were no serious adverse events, and no patients discontinued treatment due to adverse events. Seven patients (35%) showed clinical improvement, 10 (50%) had stable disease, and 3 (15%) continued to deteriorate. Significant improvements from baseline were observed in NDS in both the intent-to-treat and per protocol analyses (p=0.0005). For CG, significant improvement from baseline was observed in the per protocol analysis (p<0.05) but not in the intent-to-treat analysis. There was no significant effect of treatment on GS. Clinical improvement was not dependent on age, gender, clinical form of CIDP, or duration of symptoms. Electrophysiologic data showed improvements in mean median, ulnar, and tibial motor nerve potential areas. There was no correlation between clinical improvement and electrophysiologic data. The promising results of this study, especially given the refractory nature of the patient population, suggest that a larger placebo-controlled study should be performed to further evaluate the efficacy of IM IFNbeta-1a for the treatment of CIDP.
Subject(s)
Adjuvants, Immunologic/therapeutic use , Interferon-beta/therapeutic use , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/drug therapy , Adjuvants, Immunologic/adverse effects , Adult , Aged , Combined Modality Therapy , Electrophysiology , Female , Humans , Immunoglobulins, Intravenous/therapeutic use , Interferon beta-1a , Interferon-beta/adverse effects , Male , Middle Aged , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/physiopathology , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/therapy , Prospective Studies , Safety , Severity of Illness Index , Treatment OutcomeABSTRACT
The purpose of this study was to investigate whether the central nervous system (CNS) motor program subserving most-rapid voluntary force pulse generation is modified according to the level of agonist muscle load maintained prior to the pulse. Five normal subjects produced most-rapid force pulses to a target of 20% maximum voluntary force (MVF) above different levels of steady tonic contraction. Time to reach peak force, the first agonist burst duration and area were relatively constant for loads up to approximately 40% of MVF and then increased substantially with larger loads. These results indicate that the CNS adjusts agonist burst amplitude and duration in order to accomplish the same rapid motor task depending on the load. It is argued that these adjustments are necessary to compensate for physiological limitations of motor unit behavior and non-linearity between EMG activity and phasic force output.
