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Biomedical subjects

Mary Kay Floeter

Publications and source records attributed to Mary Kay Floeter.

12 recordsLinked to original sources
PubMed2007

Terminal latency index in neuropathy with antibodies against myelin-associated glycoproteins.

Neuropathy with antibodies against myelin-associated glycoproteins (MAG/SGPG-N) and hereditary sensorimotor neuropathy type 1 (HMSN1) are characterized by chronic demyelination with little conduction block. Electrodiagnostic studies suggest that in HMSN1 conduction slowing occurs uniformly along the nerve, whereas in MAG/SGPG-N it is predominantly distal. Some but not all previous reports have shown that the terminal latency index (TLI) was useful to distinguish MAG/SGPG-N from chronic idiopathic demyelinating polyneuropathy. We compared median TLI from 21 patients with MAG/SGPG-N with those obtained from 26 patients with HMSN1, 20 with HMSN2, and 12 healthy volunteers. All patients with TLI <0.26 had MAG/SGPG-N, and all patients with TLI > or =0.32 had HMSN1. In the remaining patients with intermediate TLI values, ulnar distal motor latency (DML) aided in differentiation between MAG/SGPG-N and HMSN1 with an overall sensitivity of 100% and specificity of 98%. In conclusion, median TLI in combination with ulnar DML can further guide the demyelinating neuropathy evaluation toward hereditary or autoimmune causes.

Action Potentials↗
PubMed2006

Movement-related cortical potentials in primary lateral sclerosis.

OBJECTIVE: Some patients with primary lateral sclerosis (PLS) have a clinical course suggestive of a length-dependent dying-back of corticospinal axons. We measured movement-related cortical potentials (MRCPs) in these patients to determine whether cortical functions that are generated through short, intracortical connections were preserved when functions conducted by longer corticospinal projections were impaired. METHODS: An electroencephalogram was recorded from scalp electrodes of 10 PLS patients and 7 age-matched healthy control subjects as they made individual finger-tap movements on a keypad. MRCPs were derived from back-averaging the electroencephalogram to the movement. RESULTS: MRCPs produced by finger taps were markedly reduced in PLS patients, including components generated by premotor areas of the cortex as well as the primary motor cortex. In contrast, the beta-band event-related desynchronization from the motor cortex was preserved. INTERPRETATION: These findings suggest that impairment in PLS is not limited to the distal axons of corticospinal neurons, but also affects neurons within the primary motor cortex and premotor cortical areas. The loss of the MRCP may serve as a useful marker of upper motor neuron dysfunction. Preservation of event-related desynchronization suggests that the cells of origin differ from the large pyramidal cells that generate the MRCP.

Adult↗
PubMed2005

Motor neuron firing dysfunction in spastic patients with primary lateral sclerosis.

Patients with corticospinal tract dysfunction have slow voluntary movements with brisk stretch reflexes and spasticity. Previous studies reported reduced firing rates of motor units during voluntary contraction. To assess whether this firing behavior occurs because motor neurons do not respond normally to excitatory inputs, we studied motor units in patients with primary lateral sclerosis, a degenerative syndrome of progressive spasticity. Firing rates were measured from motor units in the wrist extensor muscles at varying levels of voluntary contraction < or =10% maximal force. At each force level, the firing rate was measured with and without added muscle vibration, a maneuver that repetitively activates muscle spindles. In motor units from age-matched control subjects, the firing rate increased with successively stronger contractions as well as with the addition of vibration at each force level. In patients with primary lateral sclerosis, motor-unit firing rates remained stable, or in some cases declined, with progressively stronger contractions or with muscle vibration. We conclude that excitatory inputs produce a blunted response in motor neurons in patients with primary lateral sclerosis compared with age-matched controls. The potential explanations include abnormal activation of voltage-activated channels that produce stable membrane plateaus at low voltages, abnormal recruitment of the motor pool, or tonic inhibition of motor neurons.

Action Potentials↗
PubMed2005

Distal spinal and bulbar muscular atrophy caused by dynactin mutation.

Impaired axonal transport has been postulated to play a role in the pathophysiology of multiple neurodegenerative disorders. In this report, we describe the results of clinical and neuropathological studies in a family with an inherited form of motor neuron disease caused by mutation in the p150Glued subunit of dynactin, a microtubule motor protein essential for retrograde axonal transport. Affected family members had a distinct clinical phenotype characterized by early bilateral vocal fold paralysis affecting the adductor and abductor laryngeal muscles. They later experienced weakness and atrophy in the face, hands, and distal legs. The extremity involvement was greater in the hands than in the legs, and it had a particular predilection for the thenar muscles. No clinical or electrophysiological sensory abnormality existed; however, skin biopsy results showed morphological abnormalities of epidermal nerve fibers. An autopsy study of one patient showed motor neuron degeneration and axonal loss in the ventral horn of the spinal cord and hypoglossal nucleus of the medulla. Immunohistochemistry showed abnormal inclusions of dynactin and dynein in motor neurons. This mutation of dynactin, a ubiquitously expressed protein, causes a unique pattern of motor neuron degeneration that is associated with the accumulation of dynein and dynactin in neuronal inclusions.

Action Potentials↗
PubMed2004

Do F-wave measurements detect changes in motor neuron excitability?

The use of F waves to assess motor neuron excitability in experimental paradigms has never been validated. Our objective was to determine whether F-wave area, amplitude, and persistence measurements change in response to manipulations known to alter the excitability of motor neurons. The effects of muscle vibration, contraction of a remote muscle, and high-intensity stimulation of ipsilateral or contralateral fingers were assessed in 12 healthy volunteers. F-wave area, amplitude, and persistence all declined with ipsilateral cutaneous stimulation. The other maneuvers facilitated some, but not all, of the F-wave measurements. Changes in F-wave area and amplitude were correlated, but neither correlated with changes in persistence. A sample size of 50-75 F waves was needed to approximate amplitude and area results from 100 F waves with an accuracy of +/- 25%. We conclude that changes in F waves are better at detecting inhibition than facilitation of motor neurons. F waves reflect motor neuron excitability in a general way but do not allow for accurate measures of short-term changes in excitability.

Action Potentials↗
PubMed2003

Patterned sensory stimulation induces plasticity in reciprocal ia inhibition in humans.

Training of spinal cord circuits using sensorimotor stimulation has been proposed as a strategy to improve movement after spinal injury. How sensory stimulation may lead to long-lasting changes is not well understood. We studied whether sensory stimulation might induce changes in the strength of a specific spinal interneuronal circuit: spinally mediated reciprocal Ia inhibition. In healthy humans, the strength of reciprocal inhibition between ankle flexor and extensor muscles was assessed before and after 30 min of peroneal nerve stimulation at motor threshold intensity. Three stimulation protocols were assessed: patterned nerve stimulation (10 pulses at 100 Hz every 1.5 sec), uniform nerve stimulation (one pulse every 150 msec), and combined stimulation of the peroneal nerve and the motor cortex with transcranial magnetic stimulation. Short-latency reciprocal inhibition from ankle flexor to extensor muscles was measured by conditioning the soleus H-reflex with stimulation of the common peroneal nerve. The strength of the reciprocal inhibition was measured at baseline and for 20 min after each stimulation session. Patterned stimulation, with or without motor cortex stimulation, enhanced reciprocal inhibition for at least 5 min afterward. The uniform pattern of stimulation was ineffective. These results demonstrate the presence of short-term plasticity within spinal inhibitory circuits. We conclude that the pattern of sensory input is a crucial factor for inducing changes in the spinal circuit for reciprocal inhibition in humans. These findings may have implications for the use of repetitive patterned sensory stimulation in rehabilitative efforts to improve walking ability in patients with spinal injury.

Adult↗
PubMed2003

Mutant dynactin in motor neuron disease.

Impaired axonal transport in motor neurons has been proposed as a mechanism for neuronal degeneration in motor neuron disease. Here we show linkage of a lower motor neuron disease to a region of 4 Mb at chromosome 2p13. Mutation analysis of a gene in this interval that encodes the largest subunit of the axonal transport protein dynactin showed a single base-pair change resulting in an amino-acid substitution that is predicted to distort the folding of dynactin's microtubule-binding domain. Binding assays show decreased binding of the mutant protein to microtubules. Our results show that dysfunction of dynactin-mediated transport can lead to human motor neuron disease.

Amino Acid Motifs↗
PubMed2003

Cutaneous silent periods.

The cutaneous silent period (CSP) refers to the brief interruption in voluntary contraction that follows strong electrical stimulation of a cutaneous nerve. The CSP is a protective reflex that is mediated by spinal inhibitory circuits and is reinforced in part by parallel modulation of the motor cortex. This review summarizes current understanding of the afferents and circuits that are responsible for producing CSPs; the utility of the CSP for investigating peripheral and central nervous system disorders; and the relationship between the CSP, other cutaneous reflexes, and peripheral silent periods.

Afferent Pathways↗
PubMed2003

Enzyme replacement therapy improves peripheral nerve and sweat function in Fabry disease.

Fabry disease is an X-linked disorder caused by a deficiency of lysosomal alpha-galactosidase A resulting in accumulation of alpha-D-galatosyl conjugated glycosphingolipids. Clinical manifestations include a small-fiber neuropathy associated with debilitating pain and hypohidrosis. We report the effect of a 3-year open-label extension of a previously reported 6-month placebo-controlled enzyme replacement therapy (ERT) trial in which 26 hemizygous patients with Fabry disease received 0.2 mg/kg of alpha-galactosidase A every 2 weeks. The effect of ERT on neuropathic pain scores while off pain medications, quantitative sensory testing, quantitative sudomotor axon reflex test (QSART), and thermoregulatory sweat test (TST) is reported. In the patients who crossed-over from placebo to ERT (n = 10), mean pain-at-its-worst scores on a 0-10 scale decreased (from 6.9 to 4.5). There was a significant reduction in the threshold for cold and warm sensation in the foot. At the 3-year time-point, pre-ERT sweat excretion in 17 Fabry patients was 0.24 +/- 0.33 microl/mm(2) vs. 1.05 +/- 0.81 in concurrent controls (n = 38). Sweat function improved 24-72 h post-enzyme infusion (0.57 +/- 0.71 microl/mm(2)) and normalized in four anhidrotic patients. TST confirmed the QSART results. We conclude that prolonged ERT in Fabry disease leads to a modest but significant improvement in the clinical manifestations of the small-fiber neuropathy associated with this disorder. QSART may be useful to further optimize the dose and frequency of ERT.

Adult↗
PubMed2002

Increased brainstem excitability in stiff-person syndrome.

The recovery cycle of the R2 component of the blink reflex was studied in five patients with stiff-person syndrome (SPS) and in seven healthy control subjects. R2 recovery was enhanced in patients with SPS. This result is suggestive of hyperexcitability of brainstem interneuronal circuits in SPS. Hyperexcitability may result from abnormal input from suprasegmental structures or loss of inhibition by interneurons and is compatible with the proposal that there is a widespread dysfunction of central inhibitory mechanisms in SPS.

Adult↗
PubMed2002

Acute oxaliplatin-induced peripheral nerve hyperexcitability.

PURPOSE: Oxaliplatin is a novel platinum compound with clinical activity in several malignancies. Neurotoxicity is dose-limiting and occurs in two distinct forms, an acute neurologic symptom complex that occurs within hours or days of therapy and a chronic, cumulative sensory neuropathy. PATIENTS AND METHODS: Patients were treated in a phase I study designed to establish the maximum-tolerated dose of capecitabine given with oxaliplatin. Because of the unusual neurosensory toxicity of oxaliplatin, detailed neurologic examination, needle electromyography (EMG), and nerve conduction studies (NCS) were performed before and the day after oxaliplatin in a subset of 13 patients. Carbamazepine therapy was tried in 12 additional patients to determine whether the neurologic effects might be relieved. RESULTS: All patients experienced acute, reversible neurotoxicities with oxaliplatin. Symptoms included paresthesias, dysesthesias, cold hypersensitivity, jaw pain, eye pain, pain in the arm used for drug infusion, ptosis, leg cramps, and visual and voice changes. Serial EMG and NCS revealed striking signs of hyperexcitability in motor nerves after oxaliplatin. In patients who achieved therapeutic levels, carbamazepine did not alter the clinical or electromyographic abnormalities. CONCLUSION: The acute neurotoxicity seen with oxaliplatin is characterized by peripheral-nerve hyperexcitability, and the findings are similar to the clinical manifestations of neuromyotonia. Carbamezepine, which provides symptomatic relief in acquired neuromytonia, did not seem to be beneficial. Efforts to identify a successful neuroprotectant strategy would have a major impact on improving patient quality of life and the ability to deliver full doses of oxaliplatin.

Acute Disease↗