Aminopyridines are potassium channel blockers that increase the excitability of nerve cells and axons; therefore, they are widely used to treat different neurological disorders. Here we present a patient with idiopathic downbeat nystagmus and lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia who was treated with the sustained-release form of 4-aminopyridine (4-AP). During treatment with 4-AP, the LUTS improved. This improvement was monitored by using uroflowmetry and the International Prostate Symptom Score. A significant improvement of symptoms was observed in relation to the voided volume. This included an improved emptying of the bladder without an increase in residual urine. In animal studies, both nonselective K+ channel blockade and selective voltage-sensitive potassium blockade by 4-AP resulted in increased contraction on rat detrusor strips. To our knowledge, this is the first clinical observation of the mode of action of 4-AP in urological symptoms in humans.
4-Aminopyridine* ; Aminopyridines ; Animals ; Axons ; Drug Therapy ; Humans ; Lower Urinary Tract Symptoms* ; Nervous System Diseases ; Neurons ; Potassium ; Potassium Channel Blockers ; Prostate ; Prostatic Hyperplasia* ; Rats ; Urinary Bladder ; Urinary Bladder, Neurogenic

BACKGROUND AND OBJECTIVES: The transplantation of human umbilical cord blood cells (hUCBCs) has been shown to attenuate the unregulated activation of microglia in a rat model of cerebral palsy (CP). To investigate whether hUCBCs transplantation is also anti-inflammatory in humans, we performed a clinical trial in patients with CP. METHODS AND RESULTS: Allogeneic or autologous hUCBCs and erythropoietin (EPO) were intravenously injected into human patients with CP (mean age of approximately 38 weeks), and patients were analyzed for their motor function and social behavior. Blood samples were tested for cytokine levels. The most surprising finding in the study was that the cytokine levels were dependent on the donor cell source (allogeneic or autologous). Interestingly, the allogeneic treatment group demonstrated significantly decreased levels of pro-inflammatory factors, such as IL-1alpha, IL-6, TNF-beta, and RANTES, and showed a statistically significant improvement in motor and social behavior compared to the autologous treatment group. CONCLUSIONS: Given that inflammation plays a pivotal role in CP, our results suggest that allogeneic hUCBCs therapy may be an appropriate strategy for CP treatment. In addition, prior to transplantation, a detailed analysis of the amount of proinflammatory cytokines in cord blood may be needed to avoid exacerbating inflammatory responses.
Animals ; Cerebral Palsy ; Chemokine CCL5 ; Cytokines ; Erythropoietin ; Fetal Blood ; Humans ; Inflammation ; Interleukin-6 ; Lymphotoxin-alpha ; Microglia ; Rats ; Social Behavior ; Tissue Donors ; Transplants ; Umbilical Cord

BACKGROUND AND PURPOSE: Conflicting results about vestibular function in progressive supranuclear palsy (PSP) prompted a systematic examination of the semicircular canal function, otolith function, and postural stability. METHODS: Sixteen patients with probable PSP [9 females, age=72±6 years (mean±SD), mean disease duration=3.6 years, and mean PSP Rating Scale score=31] and 17 age-matched controls were examined using the video head impulse test, caloric testing, ocular and cervical vestibular evoked myogenic potentials (o- and cVEMPs), video-oculography, and posturography. RESULTS: There was no evidence of impaired function of the angular vestibulo-ocular reflex (gain=1.0±0.1), and caloric testing also produced normal findings. In terms of otolith function, there was no significant difference between PSP patients and controls in the absolute peakto-peak amplitude of the oVEMP (13.5±7.2 µV and 12.5±5.6 µV, respectively; p=0.8) or the corrected peak-to-peak amplitude of the cVEMP (0.6±0.3 µV and 0.5±0.2 µV, p=0.3). The total root-mean-square body sway was significantly increased in patients with PSP compared to controls (eyes open/head straight/hard platform: 9.3±3.7 m/min and 6.9±2.1 m/min, respectively; p=0.032). As expected, the saccade velocities were significantly lower in PSP patients than in controls: horizontal, 234±92°/sec and 442±66°/sec, respectively; downward, 109±105°/sec and 344±72°/sec; and upward, 121±110°/sec and 348±78°/sec (all p<0.01). CONCLUSIONS: We found no evidence of impairment of either high- or low-frequency semicircular function or otolith organ function in the examined PSP patients. It therefore appears that other causes such as degeneration of supratentorial pathways lead to postural imbalance and falls in patients with PSP.
Accidental Falls ; Caloric Tests ; Female ; Head Impulse Test ; Humans ; Movement Disorders ; Otolithic Membrane ; Reflex, Vestibulo-Ocular ; Saccades ; Semicircular Canals ; Supranuclear Palsy, Progressive ; Tauopathies ; Vestibular Evoked Myogenic Potentials

This paper presents diagnostic criteria for Meniere's disease jointly formulated by the Classification Committee of the Barany Society, The Japan Society for Equilibrium Research, the European Academy of Otology and Neurotology, the Equilibrium Committee of the American Academy of Otolaryngology-Head and Neck Surgery, and the Korean Balance Society. The classification includes two categories: definite Meniere's disease and probable Meniere's disease. The diagnosis of definite Meniere's disease is based on clinical criteria and requires the observation of an episodic vertigo syndrome associated with low- to medium- frequency sensorineural hearing loss and fluctuating aural symptoms (hearing, tinnitus and/or fullness) in the affected ear. Duration of vertigo episodes is limited to a period between 20 minutes and 12 hours. Probable Meniere's disease is a broader concept defined by episodic vestibular symptoms (vertigo or dizziness) associated with fluctuating aural symptoms occurring in a period from 20 minutes to 24 hours.
Classification ; Diagnosis ; Ear ; Hearing Loss, Sensorineural ; Japan ; Meniere Disease ; Neck ; Neurotology ; Otolaryngology ; Tinnitus ; Vertigo