Inhibitors of prostaglandin synthesis or cathepsin B prevent muscle wasting due to sepsis in the rat.

Systemic infection with Streptococcus pneumoniae produced atrophy, decreased twitch and tetanic tension, and altered intracellular electrolyte composition in rat skeletal muscle. Cathepsin B activity was selectively elevated early in the course of illness. Luepeptin, a cathepsin B inhibitor, and indomethacin, a prostaglandin synthesis inhibitor, prevented muscle atrophy and impaired contractility. Indomethacin, but not leupeptin, prevented the intracellular electrolyte changes. Acetaminophen reduced fever but did not prevent muscle atrophy, impaired contractility, or altered intracellular electrolytes. Muscle wasting and impaired contractility associated with sepsis may involve selective prostaglandin stimulation of cathepsin B activity. Intracellular electrolyte changes may involve prostaglandin synthesis but do not require cathepsin B activation.

Viral studies in benign acute childhood myositis.

Thirty-five cases of benign acute childhood myositis followed infections with influenza A or B. Two children had recurrent myositis associated with infections of different influenza types. None of the children had acute-phase antibody titers to the infecting type of influenza. These results are consistent with the proposal that benign acute childhood myositis can occur only with the initial infection of a viral type.

Insulin acts in hypokalemic periodic paralysis by reducing inward rectifier K+ current.

OBJECTIVE: To define how insulin acts in hypokalemic periodic paralysis (HypoPP). BACKGROUND: HypoPP results from point mutations of the skeletal muscle L-type Ca2+ channel. Attacks of flaccid paralysis are associated with hypokalemia and triggered by insulin. A persistent inward current causes depolarization-induced paralysis. The relationships of the Ca2+ channel mutations to the persistent inward current and how insulin triggers paralytic attacks are not yet known. METHODS: Intercostal muscle fibers from HypoPP and normal subjects were studied in vitro at 37 degrees C using two electrodes to determine action potential thresholds and a three-electrode voltage clamp to study membrane currents. RESULTS: HypoPP fibers were depolarized in bathing solution with 4 mM K+. Reducing K+ from 4.0 mM to 2.5 or 1.0 mM depolarized HypoPP fibers but hyperpolarized normal fibers. Adding 12 mU/mL of insulin to bathing fluids increased the depolarization of HypoPP fibers and increased the hyperpolarization of normal fibers. Depolarized HypoPP had increased action potential thresholds. The fraction of excitable muscle fibers decreased with increasing fiber depolarization. Blocking Na+ channels or L-type Ca2+ channels did not prevent depolarization induced by hypokalemia or by insulin. Insulin reduced the conductance of the inward rectifier K+ channel for outward-flowing currents. CONCLUSIONS: Insulin potentiates depolarization of hypokalemic periodic paralysis (HypoPP) fibers by reducing inward rectifier K+ conductance. The Ca2+ mutations in HypoPP indirectly derange membrane excitability by altering the function of other membrane channels.

Dissociated weakness of sternocleidomastoid and trapezius muscles with lesions in the CNS.

We describe three patients with lesions in the CNS that produced dissociated weakness of trapezius (TM) and sternocleidomastoid muscles (SCM). One patient with a right cerebral hemisphere lesion had left TM weakness and right SCM weakness. A second, with a brainstem lesion, and a third, with a high cervical cord lesion, had TM weakness with preserved SCM strength. We discuss the findings according to the known neuroanatomy.

Aphemia resulting from a left frontal hematoma.

A 15-year-old right-handed woman had selective impairment of speech--aphemia--after drainage of a left frontal hematoma caused by an arteriovenous malformation. There was no buccofacial or pharyngeal muscle dysfunction. Computerized tomography demonstrated residual injury extending from the Broca area to the inferior left precentral gyrus. Aphemia may have resulted from disruption of the connection between Broca's area and the portion of the motor cortex that controls oral and pharyngeal muscles.

Evaluation of acute cerebral ischemia for anticoagulant therapy: computed tomography or lumbar puncture.

Of 217 patients with clinical diagnosis of acute stroke 23% had nonischemic lesions diagnosed by computed tomography (CT) or lumbar puncture (LP). CT demonstrated all 37 cases of intracerebral hemorrhagic lesions; 9 were detected by LP. CT failed to demonstrate 8 of 17 cases of subarachnoid hemorrhage, but only 1 of these lacked headache or stiff neck. In 7 of 342 patients who were treated with anticoagulants after LP, spinal hematoma followed LP ( 5 with paraparesis). CT evaluation reduced the incidence of fatal cerebral hemorrhage during anticoagulant therapy of acute stroke. However, even if patients were evaluated with both CT and LP, the incidence of fatal cerebral hemorrhage resulting from intravenous anticoagulant therapy was 2.4%.

Pneumatic sequential compression reduces the risk of deep vein thrombosis in stroke patients.

OBJECTIVE: To determine if pneumatic sequential compression devices (SCDs) combined with subcutaneous heparin and antiembolic hose reduce the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) in stroke patients. BACKGROUND: DVTs and PEs are serious complications among hospitalized stroke patients. Subcutaneous heparin and SCDs have both been used to prevent DVT. It is not known if SCDs combined with subcutaneous heparin can improve the protection afforded by heparin alone. METHODS: The study group was comprised of nonhemorrhagic stroke patients admitted to the neurology service from October 1988 through June 1996. From October 1988 through April 1991 (233 patients), and during February 1993 (16 patients), patients received 5,000 U subcutaneous heparin twice daily and antiembolic hose. From June 1991 through January 1993 and from March 1993 through June 1996 (432 patients) all nonambulatory stroke patients had SCDs applied to both legs in addition to subcutaneous heparin and antiembolic hose. RESULTS: Twenty-three of 249 patients (9.2%; 21 of 233 and two of 16 patients) treated with heparin alone developed DVT and six patients (2.4%) developed PE (six of 233 and zero of 16). Half the PE cases (three of six) were fatal and all PEs were in patients with DVT. Eighty-three of the 249 patients were nonambulatory. Twenty-two of the 23 DVTs and all the PEs developed in nonambulatory patients. Only one DVT (0.23%) and no PEs occurred among the 432 patients (148 nonambulatory) treated with SCDs as well as heparin. The addition of SCDs resulted in more than a 40-fold reduction in the risk of DVT. CONCLUSIONS: Nonambulatory stroke patients have an increased risk for DVT and PE. Adding SCDs to treatment with subcutaneous heparin and antiembolic hose reduced the risks of DVTs and PEs. SCDs should be considered for adjunctive DVT prophylaxis in nonambulatory stroke patients.

Second occurrence of spinal epidural metastases.

We reviewed records of 79 men with spinal epidural metastases diagnosed from July 1984 to July 1989, imaged by myelography or MRI, and treated with radiation therapy. Thirteen men (16%) had second epidural metastases. The mean time between lesions that developed within two vertebral bodies of a prior lesion was 2.8 months, compared with 15.2 months for lesions that were three or more vertebral bodies from a prior lesion. Some secondary spinal metastases occurring soon after the initial metastasis may represent regrowth of tumor at the border of the radiation port, suggesting that larger radiation ports be constructed for patients with lengthy expected survival times.

A case of persistent cortical deafness: clinical, neurophysiologic, and neuropathologic observations.

A 61-year-old man became deaf after the second of two cerebral infarctions which successively involved the temporal and adjacent cortices. He remained completely deaf until death 27 months later. Click stimulation demonstrated normal short-latency potentials, middle-latency responses better developed to stimulation of the right than of the left ear, and absent long-latency potentials. Neuropathologic examination showed cystic infarctions involving both transverse temporal gyri and adjacent cortical areas with preservation of the brainstem auditory nuclei. Persistent deafness can result from bilateral lesions involving the auditory and adjoining cortices.

Effect of anticholinergic agents upon acquired nystagmus: a double-blind study of trihexyphenidyl and tridihexethyl chloride.

We conducted a randomized, double-blind, crossover trial of two anticholinergic agents--trihexyphenidyl and tridihexethyl chloride (a quaternary anticholinergic that does not cross the blood-brain barrier)--in patients with acquired nystagmus and measured visual acuity and nystagmus before and at the end of 1 month on each medication. Of the 10 patients admitted to the study, only five completed trials of both drugs due to intolerance of medication or intercurrent illness. Of six patients who completed the trial of trihexyphenidyl, only one showed improvement. Of six patients who completed a trial of tridihexethyl chloride, four showed improvement. We conclude that (1) trihexyphenidyl is not a reliable treatment for acquired nystagmus, although occasional patients may benefit; (2) anticholinergic agents may suppress nystagmus by peripheral rather than central mechanisms; and (3) the side effects of anticholinergic agents limit their effectiveness in the treatment of nystagmus.

Asymmetry of forearm rolling as a sign of unilateral cerebral dysfunction.

We compared the reliability of asymmetry of forearm rolling (rotation of one forearm around the other in front of the torso) as a sign of unilateral cerebral dysfunction with that of other standard clinical tests. We studied 62 patients with radiologically confirmed unilateral cerebral lesions and 20 control subjects with normal imaging. Asymmetric forearm rolling was the most sensitive indicator of unilateral hemispheric disease (85%). This simple test is a useful addition to the neurologic examination.

The gamma-subunit of the acetylcholine receptor is not expressed in the levator palpebrae superioris.

In extraocular muscle (EOM), expression of the gamma-subunit, which is associated with the fetal-type acetylcholine receptor (AChR), may offer a differential target for immune-mediated damage and could explain the preponderance of ocular manifestations caused by myasthenia gravis (MG). Using Poly(A)+ RNA hybridization, we investigated expression of the gamma-subunit in bovine levator palpebrae superioris (LP), a muscle also differentially involved by MG. There were no transcripts of the gamma-subunit of the AChR, but the epsilon-subunit, associated with the adult-type AChR, was present. The results indicate that the susceptibility of LP to MG is not mediated by gamma-subunit expression and suggest that multiterminal fibers in EOM may be the site of gamma-subunit expression.

Disorders of neuromuscular junction ion channels.

Ion channel defects produce a clinically diverse set of disorders that range from cystic fibrosis and some forms of migraine to renal tubular defects and episodic ataxias. This review discusses diseases related to impaired function of the skeletal muscle acetylcholine receptor and calcium channels of the motor nerve terminal. Myasthenia gravis is an autoimmune disease caused by antibodies directed toward the skeletal muscle acetylcholine receptor that compromise neuromuscular transmission. Congenital myasthenias are genetic disorders, a subset of which are caused by mutations of the acetylcholine receptor. Lambert-Eaton myasthenic syndrome is an immune disorder characterized by impaired synaptic vesicle release likely related to a defect of calcium influx. The disorders will illustrate new insights into synaptic transmission and ion channel structure that are relevant for all ion channel disorders.

Magnetic resonance imaging in patients with diplopia. A review.

Magnetic resonance imaging may be the procedure of choice for evaluating patients with diplopia; the absence of signals from cortical bone enables the brain stem and individual cranial nerves to be visualized and the imaging planes selected easily, and there is excellent contrast resolution of pathologic lesions. A clinical assessment of diplopia including the identification of associated neurologic disturbances is necessary prior to MR imaging, however, to assure that appropriate anatomic areas are studied and imaging sessions kept within acceptable time limits. The relevant physiology and anatomy critical to normal ocular motility are reviewed and the value of MR imaging for diplopia demonstrated by selected patient examples.

Electrophysiology of postsynaptic activation.

The safety factor for neuromuscular transmission depends upon the amount of ACh released from the nerve terminal, the number of AChRs, and the concentration of Na+ channels at the end plate potential. The postsynaptic end plate membrane of the neuromuscular junctions is specialized in three ways: (1) AChRs, Na+ channels, ChE, NOS, and other membrane-associated proteins are concentrated at the end plate; (2) the end plate cytoskeleton has a different composition of proteins as compared with extrajunctional membrane; and (3) the end plate membrane is mechanically different as compared with extrajunctional membrane. A blockade of neuromuscular transmission occurs when ACh release is inadequate or the end plate response to ACh is too small to trigger an AP. A safety factor for neuromuscular transmission exists because the EPP is larger than the threshold for generating an AP. The high concentration of Na+ channels at the end plate increases the safety factor for neuromuscular transmission by reducing the threshold depolarization required to initiate an AP. In MG, the safety factor is reduced due to loss of AChRs and loss of Na+ channels. The loss of AChRs reduces the EPP and the Na+ channel loss increases the threshold for triggering an AP.

Myf-4 does not mediate AChR receptor subunit mRNA expression in thymic tissues.

We investigated whether a MyoD gene family member plays a role in the expression of AChR or AChR-like proteins in human thymus. We amplified from thymic tissue, mRNA of subunits of the fetal- and adult-type AChR, and Myf-4, a gene product that appears to regulate AChR expression. RNA extracted from paraffin-embedded thymic tissue of five myasthenics and five nonmyasthenics was subjected to reverse transcription followed by polymerase chain reaction using primers specific for these mRNAs. Thymic RNA from eight of ten patients contained transcripts of the alpha- and epsilon-subunits (specific for the adult-type AChR). Presence of these transcripts did not correlate with thymic pathology or clinical presentation. No gamma-subunit (specific for the fetal-type AChR) or Myf-4 transcripts were found. Our results indicate that mRNA for the adult-type AChR is expressed in thymic tissue and is expressed by mechanisms not involving Myf-4. Thymic AChR subunits may be the primary epitope that initiates the immune response in MG against the adult-type AChR.

Elevated intracellular Ca2+ and myofibrillar Ca2+ sensitivity cause iodoacetate-induced muscle contractures.

Ischemic stimulation of iodoacetic acid (IAA)-treated rat extensor digitorum longus (EDL) muscles produced contractures. Similar ischemic stimulation of control EDL muscles did not result in contracture. At the onset of contracture, ATP concentration was not reduced, phosphocreatine concentration was reduced > 75%, ADP concentration was increased 9-fold, Ca2+ concentration ([Ca2+]) was increased approximately 11-fold, and inorganic phosphate concentration increased less in IAA-treated muscles than in stimulated control muscles. To test whether contracture resulted from elevated [Ca2+] and/or increased Ca2+ sensitivity of the contractile proteins, this laboratory made skinned fiber-activating solutions that simulated four different conditions: unstimulated IAA-treated and control muscles, IAA-treated muscles at contracture, and ischemically simulated control muscles. Skinned EDL fibers had lower single-fiber tensions and reduced Ca2+ sensitivities in activating solutions that mimicked the conditions in stimulated control muscles compared with activating solutions that simulated the conditions in unstimulated muscles. In contrast, the maximum tension was maintained and Ca2+ sensitivity was increased in activating solutions that simulated contracture. Tension at contracture resulted from increased intracellular [Ca2+] and increased myofibrillar Ca2+ sensitivity compared with the Ca2+ sensitivity of stimulated control fibers.

Feasibility of gait training for acute stroke patients using FNS with implanted electrodes.

Following stroke, many patients do not regain a normal, safe gait pattern even after receiving conventional physical therapy. One promising technique is functional neuromuscular stimulation (FNS) with intramuscular (IM) electrodes (FNS-IM). Five subjects were admitted into the study at 3 weeks to 3 months following the stroke. For each subject, electrodes were placed intramuscularly at the motor point of up to seven lower extremity paretic muscles. Subjects were treated for 6 months, twice weekly with FNS-IM for exercise and gait training. The stimulator and software provided individualized stimulation patterns, with flexible stimulus parameters and activation timings of multiple muscles. Outcome measures were active joint movement, coordination (Fugl-Meyer scale), balance (Tinetti scale), gait (Tinetti scale), activities of daily living (functional independence measure), and therapist and subject satisfaction (survey instrument). Subjects tolerated well the placement of IM electrodes with no adverse effects, and subjects lost no conventional rehabilitation time. Therapists and subjects were satisfied with the FNS-IM system as a rehabilitation tool. Post treatment, subjects demonstrated improvements in impairment and disability in active joint movement, coordination, balance, gait and activities of daily living. Considered together with prior research for chronic stroke subjects, this research suggests that FNS-IM can be successfully and efficaciously utilized for gait training for those with acute stroke.

Treatment of the elderly patient with headache or trigeminal neuralgia.

The elderly as a whole suffer fewer headaches than the young. For the majority headache will represent a minor annoyance to be endured or treated with any available drug in the medicine chest. For some, migraine headaches or tension-type headaches become entwined with every daily activity. With the advent of modern pharmacology, headache can often be treated successfully. Trigeminal neuralgia is a source of particularly high morbidity among the elderly, but may be treated very satisfactorily with carbamazepine or baclofen. Paroxysmal hemicrania is exquisitely sensitive to indomethacin, while cluster headache patients receive relief from oxygen inhalation, corticosteroids or lithium. Headache may be the signature of the disease which leads to serious morbidity and mortality. The 'sentinel' headache of subarachnoid haemorrhage is evaluated by a physician in 15% of patients who will eventually rupture an intracranial aneurysm. Morning headache with nausea and vomiting may represent increased intracranial pressure caused by a tumour, haematoma or abscess. The elderly patient with a new headache needs emergency evaluation for temporal arteritis and rapid corticosteroid treatment if the diagnosis is confirmed, to prevent blindness. The broad spectrum of headache, at times a benign aggravation, while at others the harbinger of death, makes the careful evaluation of each headache imperative. This article attempts to make the difficult evaluation of head pain a little easier.

A four-drug pain regimen for head and neck cancers.

Twenty patients with end-stage head and neck cancer, unresponsive to either acetaminophen with codeine or oxycodone hydrochloride, were placed on a four-drug analgesic regimen consisting of methadone hydrochloride, Trilisate or acetaminophen, a tricyclic antidepressant, and, in most cases, hydroxyzine. All drugs could be delivered through a feeding tube, making this regimen appropriate for dysphagic patients. The efficacy of this nonparenteral regimen was assessed by structured pretreatment and posttreatment interviews that addressed pain intensity, activity, and sleep levels. All of the patients showed improvement in their pain levels and 16 of the 20 had a > or = 50% improvement in all of their pain ratings (P < .01) that persisted until death (2 to 10 months later). Excellent results and ease of administration make this regimen a good choice for analgesia in terminal patients.