A randomized trial of intravenous immunoglobulin in inflammatory demyelinating optic neuritis.

OBJECTIVE: To determine whether IV immunoglobulin (IVIg) reverses chronic visual impairment in MS patients with optic neuritis (ON). METHODS: In this double-blind, placebo-controlled Phase II trial, 55 patients with persistent acuity loss after ON were randomized to receive either IVIg 0.4 g/kg daily for 5 days followed by three single infusions monthly for 3 months, or placebo. RESULTS: The trial was terminated by the National Eye Institute because of negative results when 55 of the planned 60 patients had been enrolled. Fifty-two patients completed the scheduled infusions, and 53 patients completed 12 months of follow-up. Analysis of this data indicated that a difference between treatment groups was not observed for the primary outcome measure, improvement in logMAR visual scores at 6 months (p = 0.766). Exploratory secondary analyses suggested that IVIg treatment was associated with improvement in visual function (including logMAR visual scores at 6 months and visual fields at 6 and 12 months) in patients with clinically stable MS during the trial. CONCLUSIONS: IVIg administration does not reverse persistent visual loss from ON to a degree that merits general use.

Myasthenia, thymoma, presynaptic antibodies, and a continuum of neuromuscular hyperexcitability.

BACKGROUND: Autoantibodies specific for the nicotinic acetylcholine receptor (AChR) of skeletal muscle impair neuromuscular transmission in myasthenia gravis (MG). Autoantibodies specific for alpha3 neuronal AChRs or voltage-gated potassium channels have been reported in patients with Isaacs syndrome, an acquired disorder of continuous muscle fiber activity characterized by neuromyotonia. OBJECTIVE: To report the neuromuscular autoantibody profiles of three patients with a syndrome of MG and neuromuscular hyperexcitability. RESULTS: All three patients reported here had clinical and electrophysiologic evidence of MG and neuromuscular hyperexcitability. None had neuromyotonia. Thymoma was proven in two patients and suspected in the third. One had MG and thymoma and subsequently developed cramp-fasciculation syndrome; MG and rippling muscle syndrome appeared simultaneously in the other two. All patients had muscle and neuronal AChR binding antibodies and striational antibodies. Only one had antibodies reactive with alpha-dendrotoxin-complexed potassium channels. CONCLUSIONS: The coexistence of cramp-fasciculation syndrome and acquired rippling muscle syndrome with MG, thymoma, and neuronal AChR autoantibodies suggests that there is a continuum of autoimmune neuromuscular hyperexcitability disorders related pathogenically to Isaacs syndrome. Manifestations of neuromuscular hyperexcitability may be altered and less apparent in the context of MG because of the coexisting defect of neuromuscular transmission.

Role of the blink reflex in the evaluation of sensory neuronopathy.

Because of an incidental observation that the blink reflex was normal in paraneoplastic sensory neuronopathy (SN) and frequently abnormal in nonparaneoplastic SN, the authors reviewed the electromyographic records of patients with SN in whom blink reflex studies were performed. The blink reflex was normal in all 17 patients with paraneoplastic SN and abnormal in 20 of 43 patients with nonparaneoplastic SN. Although it does not exclude paraneoplastic SN, an abnormal blink reflex favors a nonparaneoplastic etiology.

Facial trigeminal synkinesis associated with a trigeminal schwannoma.

The authors describe the clinical and electrophysiologic findings in a patient with synkinesis between muscles innervated by the facial and trigeminal nerves after resection of a trigeminal schwannoma. Conventional facial nerve conduction and blink reflex studies were normal. Stimulation of the supraorbital and facial nerves elicited reproducible responses in the masseter and pterygoid muscles, confirming a peripheral site of aberrant regeneration of the facial and trigeminal nerves.

Role of the masseter reflex in the assessment of subacute sensory neuropathy.

In 3 patients with a severe pure sensory neuropathy of subacute onset, the masseter reflex remained normal despite absent blink reflex responses and absent stretch reflexes in the extremities. In 20 patients with primary disorders of peripheral nerve axons or myelin, the masseter reflex was abnormal. This study suggests that a normal masseter reflex in patients presenting with a pure sensory neuropathy favors a polyganglionopathy rather than a primary axonal sensory neuropathy, particularly if the blink reflex is abnormal.

Myokymic discharges of the tongue after radiation to the head and neck.

We report two patients who developed myokymic discharges of the tongue after radiation therapy. One patient had carcinoma of the nasopharynx, and the other had a chemodectoma of the middle ear. Radiation therapy may damage the hypoglossal nerve and cause myokymia of the tongue, similar to myokymic discharges associated with brachial plexopathies after radiation therapy.

AAEM minimonograph #44: diseases associated with excess motor unit activity.

Stiff-man syndrome is due to hyperexcitability of anterior horn cells, possibly related to interference with the synthesis or action of gamma-aminobutyric acid. Unexpected acoustic and exteroceptive stimuli produce exaggerated muscle responses. Needle electrode examination of involved muscles yields nonspecific findings and demonstrates involuntary motor unit activity. The appearance and firing pattern of motor units are normal except that agonist and antagonist muscles may contract concurrently. Continuous muscle fiber activity (Isaacs' syndrome) comprises a heterogeneous group of hereditary and acquired disorders that cause hyperexcitability of peripheral nerves. Some are associated with electrophysiologic evidence of peripheral neuropathy and some are not. Repetitive afterdischarges often follow the M-, H-, and F-waves. Needle electrode examination reveals an abnormal pattern of motor unit firing, consisting of myokymic discharges, doublets and multiplets, neuromyotonic discharges, and fasciculations. These abnormalities may occur alone or in combination.

Hemimasticatory spasm: clinical and electrophysiologic observations.

Hemimasticatory spasm is a rare disorder of the trigeminal nerve that produces involuntary jaw closure due to paroxysmal unilateral contraction of jaw-closing muscles. We report three patients with this disorder. Electrophysiologic studies demonstrated normal blink and masseter reflexes. The masseter inhibitory reflex was absent during periods of spasm. Needle electromyography demonstrated irregular bursts of motor unit potentials that were identical to the pattern observed in hemifacial spasm. The electrophysiologic findings suggest ectopic excitation of the trigeminal motor root or its nucleus, an abnormality that is analogous to ectopic excitation of the facial nerve in hemifacial spasm. One patient improved temporarily with surgery, one improved while on treatment with carbamazepine, and another responded favorably to botulinum toxin injection.

Management of unruptured intracranial arteriovenous malformations: a decision analysis.

The management of unruptured intracranial arteriovenous malformations (AVMs) is controversial. Some authorities favor elective excision of the AVM before it bleeds, whereas others advise nonintervention unless the AVM bleeds, at which time surgical excision is performed in those who survive. A Markov model was developed that stimulates a clinical trial in which cohorts of patients with unruptured AVMs were assigned to either elective excision of their AVMs or conservative treatment (unless the AVM bled). Incremental utilities for both strategies were calculated at the end of each year after the beginning of the trial and are expressed as quality and risk-adjusted life years. The process was continued until all members of the cohorts had died. The mean quality and risk-adjusted life expectancy for members of a cohort was calculated by dividing the total number of quality and risk-adjusted life years the cohort had accumulated by the size of the cohort. If the baseline values for surgical complications were used in the computation, the quality and risk-adjusted life expectancy for the surgical cohorts was at least 1 quality and risk-adjusted life year greater than for nonsurgical cohorts up to age 44. If a more favorable complication rate were used, elective surgery could benefit selected patients in their early 60s when the location and configuration of the AVM was favorable. Elective surgical resection is justified in many instances before rupture, particularly in young patients who have intracranial AVMs that have a favorable location, size, and venous drainage.

Preservation of the masseter reflex in Friedreich's ataxia.

In Friedreich's ataxia, the muscle stretch reflexes are absent or hypoactive in the upper and lower extremities because of pathologic involvement of the dorsal root ganglion cells. Paradoxically, the masseter reflex remains unaffected and may even be hyperactive in some cases. The masseter reflex is hypothesized as unique among stretch reflexes in that its afferent nerve cell body (the mesencephalic nucleus) is located intra-axially within the brainstem rather than in the craniospinal ganglia, where the afferent nerve cell bodies subserving the other stretch reflexes are located. This study supported this hypothesis by demonstrating that the masseter reflex is (1) usually absent in patients who are areflexic as a result of primary disorders of peripheral nerve axons or myelin, and (2) preserved in other disorders that primarily involve the dorsal root ganglion cells.

Management of unruptured intracranial aneurysms: A decision analysis.

Decision analysis was carried out to gain insight into the optimal management of patients aged 20-80 years with unruptured intracranial aneurysms between 10 and 25 mm in diameter. Baseline probabilities for outcomes resulting from either elective repair of the aneurysm or nonintervention were obtained from studies of patients with intracranial aneurysms seen at the Mayo Clinic. The utility of each outcome was based on the mean life expectancy for otherwise normal people of the same age and sex, with an adjustment made for quality of life. If these baseline probabilities and utilities are used in the calculations, elective surgical repair of unruptured aneurysms of this size is preferable to nonintervention in men under age 69 and in women under age 75 if they are otherwise in good health.

Hemifacial spasm in Rochester and Olmsted County, Minnesota, 1960 to 1984.

The incidence of hemifacial spasm in residents of Olmsted County, Minnesota, was studied by reviewing the medical records of patients residing in the community between 1960 and 1984. The average annual incidence rate was 0.74 per 100,000 in men and 0.81 per 100,000 in women, age-adjusted to the 1970 US white population. The average prevalence rate was 7.4 per 100,000 population in men and 14.5 per 100,000 in women. The incidence and prevalence rates were highest in those from 40 to 79 years of age.

Trigeminal sensory neuropathy associated with decreased oral sensation and impairment of the masseter inhibitory reflex.

We describe 4 patients with severe trigeminal sensory neuropathy whose main disability resulted from impaired intraoral sensation associated with disturbances of mastication and swallowing. Each patient had an abnormal blink reflex and jaw jerk. In addition, the masseter inhibitory reflex was absent in 3 patients and abnormal in the 4th. This reflex plays a role in the reflex control of mastication and can easily be elicited in normal subjects by stimulation of the skin and mucous membrane in the distribution of the 2nd and 3rd divisions of the trigeminal nerve while the jaw-closing muscles are contracting. Disturbed intraoral sensation combined with impaired trigeminal reflexes (particularly the masseter inhibitory reflex) interferes with neural mechanisms that regulate chewing and can be a source of severe disability in patients with trigeminal sensory neuropathy.

Hemifacial spasm associated with epidermoid tumors of the cerebellopontine angle.

Hemifacial spasm (HFS) is rarely due to serious compressive lesions, such as tumors, aneurysms, or vascular malformations, located in the cerebellopontine angle. Because of the interesting association of HFS with epidermoid tumors, we reviewed the records of all patients with HFS and all patients with intracranial epidermoid tumors seen from January 1975 to December 1986. Of the 18 patients who had epidermoid tumors of the cerebellopontine angle, 3 (17%) had a facial movement disorder that resembled HFS at sometime during their illness. There were 429 patients who had HFS with no obvious serious compressive lesion of the facial nerve. Therefore, HFS was associated with epidermoid tumor in 0.7% of cases. All 3 patients developed other findings due to involvement of adjacent neural structures. Patients with HFS have a low probability of having a serious compressive lesion, but those with atypical features should be evaluated for cerebellopontine angle masses such as epidermoid tumors.

Facial paralysis and occult parotid cancer. A characteristic syndrome.

Extratemporal involvement of the seventh cranial nerve is often secondary to a tumor of the parotid gland. We describe six patients who had facial paralysis associated with an occult malignant neoplasm of the parotid gland. Initial evaluations in these patients, including computed tomography and magnetic resonance imaging, provided no evidence of a parotid tumor. Four of the six patients had a progressive triad of ear pain, facial paralysis, and sensory loss in the second and third divisions of the trigeminal nerve. This pattern indicates a high probability of a malignant lesion of the parotid gland, even in the presence of normal findings on noninvasive studies.

Hemifacial spasm: results of microvascular decompression of the facial nerve in 54 patients.

During the 10-year period between January 1975 and December 1984, 367 patients with hemifacial spasm were examined at our institution. Because of the severity of the spasm, 54 patients underwent surgical management that consisted of microvascular decompression of the facial nerve. Postoperatively, the hemifacial spasm was completely resolved in 44 patients (81%), but 6 of these patients had subsequent recurrence of the condition. An additional five patients (9%) experienced improvement but were not totally free of the spasm. Five patients (9%) received no benefit from the procedure. Complications occurred in 19 patients (35%) but were usually transient. The most serious complication was permanent ipsilateral hearing loss, which occurred in eight patients (15%). Thus, in general, microvascular decompression of the facial nerve effectively alleviates hemifacial spasm.

Hereditary form of sustained muscle activity of peripheral nerve origin causing generalized myokymia and muscle stiffness.

Six patients in two unrelated families had a hereditary form of sustained muscle activity of peripheral nerve origin. Although varying in severity among affected family members, the disease was manifested clinically as generalized myokymia and muscle stiffness. Motor and sensory nerve conduction velocities and results of nerve biopsy were normal. Repetitive after-discharges followed each motor nerve stimulus. Needle electrode examination demonstrated spontaneous recurrent bursts of motor unit activity. The burst activity of a motor unit occurred rhythmically (0.5 to 4 bursts per second) and independently of the activity of other units. Within a burst, the firing rate was high (150 to 300 Hz). The clinical and electromyographic abnormalities improved considerably after treatment with carbamazepine or phenytoin.