Robert E. Lovelace

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) Clinical, biochemical, and genetic features of an autosomal recessive mitochondrial disorder

We studied the clinical, biochemical, and genetic features of eight patients with the autosomal recessive mitochondrial syndrome mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). MNGIE is clinically characterized by ophthalmoparesis, peripheral neuropathy, leukoencephalopathy, gastrointestinal symptoms (recurrent nausea, vomiting, or diarrhea) with intestinal dysmotility, and histologically abnormal mitochondria in muscle. Brain MRI scans were consistent with leukodystrophy in seven patients examined. Nerve conduction and EMG studies were compatible with a sensorimotor neuropathy; quantitative EMG of two patients suggested a myogenic process. Muscle mitochondrial enzyme analysis revealed a partial defect of cytochrome c oxidase activity in five patients; three had additional respiratory chain enzyme defects. Two patients had isolated complex I defects, and one had normal respiratory chain function. Southern blot analysis revealed multiple deletions of mitochondrial DNA in four of eight patients.

The spectrum of neurologic disease associated with anti‐GM1 antibodies

We compared anti-GM1 IgM antibody titers in patients with various neurologic diseases and in normal subjects. We found increased titers in patients with lower motor neuron disease, sensorimotor neuropathy, or motor neuropathy with or without multifocal conduction block. In patients with other diseases, titers are similar to those in normal individuals, suggesting that anti-GM1 antibody levels are not increased nonspecifically after neural injury or inflammatory diseases. Anti-GM1 antibodies in many of the patients occur as monoclonal gammopathies, predominantly of lambda light-chain type, but the antibodies are sometimes polyclonal with normal or increased serum IgM concentrations. Most of the anti-GM1 antibodies appear to react with the Gal(β1-3)GalNAc epitope which is shared with asialo-GM1 and GD1b, but in some patients the antibodies are more specific for GM1 and associated with motor neuropathy. Patients with motor or sensorimotor peripheral neuropathy or lower motor neuron disease should be tested for anti-GM1 antibodies or anti-Gal(β1-3)GalNAc antibodies, as therapeutic reduction in antibody concentrations was reported to result in clinical improvement in some patients.

Localized injections of botulinum toxin for the treatment of focal laryngeal dystonia (spastic dysphonia)

Spastic dysphonia is a condition producing a strain‐strangle phonation. We have previously classified most of these patients as having focal laryngeal dystonia, a disorder of central motor processing.

The sympathetic skin response: normal values, elucidation of afferent components and application limits

The sympathetic skin response (SSR), recorded at the hand and foot, was elicited using different classes of stimuli in 20 normal controls and 10 patients with peripheral neuropathy. We found that SSR latencies changed significantly with different recording sites, but not with different stimulation sites. Additionally, after ischemic conduction block of the arm in 3 normal controls, the previously obtainable SSR recorded at the hand became unobtainable with median nerve stimulation. Also, in one patient with subacute ganglionitis and 3 patients with demyelinating neuropathies, the SSR could not be elicited by electrical stimulation, but it could with deep inspiration. These results suggest that large diameter myelinated fibers may serve as afferents for the SSR. Furthermore, these findings imply that an unobtainable SSR by electrical stimulation may be due not only to dysfunction of the autonomic efferent nerve fibers, but also to abnormalities of the sensory afferents of the reflex. Therefore, investigations of autonomic dysfunction utilizing the SSR must be interpreted with caution in patients with peripheral neuropathies.

Clinical and laboratory characteristics of focal laryngeal dystonia: Study of 110 cases

Spastic dysphonia is a syndrome often, producing a strain‐strangle voice. We have previously classified most of these patients as having focal laryngeal dystonia, a disorder of central motor processing. In a study of 1,280 cases of dystonia registered at the Dystonia Clinical Research Center at the Columbia‐Presbyterian Medical Center, we found 110 patients who had vocal cord involvement.

Electromyographic Findings in Focal Laryngeal Dystonia (Spastic Dysphonia)

Spastic dysphonia is a clinical speech disorder characterized by spasms of the laryngeal muscles during phonation, producing a broken pattern of speech sometimes termed laryngeal stuttering. Fourteen patients with the diagnosis of spastic dysphonia based on voice quality were referred for evaluation; detailed clinical and electrophysiologic evaluations were performed. Laryngeal electromyographic (EMG) testing failed to demonstrate any spontaneous activity in the 14 patients tested. Seven patients (50 %) had normal number and amplitude of motor unit potentials. Four of these had disparate amplitudes when compared with the other side, and two had complex motor unit potentials. The other seven patients (50 %) had abnormal findings, including three patients with abnormally increased amplitude. Two patients had asynchronous activity characteristic of a tremor disorder. One patient had synchronous bursts of activity also affecting the diaphragm, later diagnosed as pyramidal and extrapyramidal disease. One patient had bursts of activity, and later presented with diffuse myoclonus. Laryngeal EMG therefore seemed to be a more precise way of evaluating patients presenting with a tremulous voice pattern termed spastic dysphonia. Clinical observation and EMG data demonstrated that spastic dysphonia is not a “spastic” disease. We identified patients with tremor (2), pyramidal and extrapyramidal disease (1), and myoclonic disorders (1). The remainder of the patients had clinical and EMG findings consistent with dystonia, a neurologic disorder characterized by abnormal, often action-induced, involuntary movements or uncontrolled spasms. We classify these patients as having “focal laryngeal dystonia” when the disorder occurs in isolation. It may also present as a component of a generalized dystonic syndrome.

Motor neuron disease and plasma cell dyscrasia

In the years 1977 to 1984, 10 of 206 patients (4.8%) with motor neuron disease (MND) had M proteins; 4 had IgM and 6 had IgG. Among 100 control patients with other neurologic diseases, only 1 had an M protein. We later added six cases of MND and M proteins, as well as three with polyclonal IgM elevations and two with Bence-Jones proteins. Including other reports, there are now 37 known cases of MND with monoclonal and 5 with polyclonal gammopathy. There is evidence that plasma cell dyscrasia is often undetected; the actual incidence of serum immunoglobulin abnormality in patients with MND may be greater than our figure.

A Rational Approach to Total Thymectomy in the Treatment of Myasthenia Gravis

Thymectomy is important in the treatment of myasthenia gravis. Total removal of the gland is considered indicated. Although median sternotomy has been the accepted surgical procedure, the transcervical approach has been advocated as a safer method of achieving total thymectomy. A surgical-anatomical study of the thymus was made in 22 patients. A high incidence of surgically important variations in thymic anatomy was found in the neck and in the mediastinum. We believe wide exposure by way of median sternotomy with direct vision is required to remove all of the extracapsular mediastinal thymus in many patients, and good cervical exposure is required to remove the anomalous tissue in the neck. If a total thymectomy is to be achieved, we recommend a median sternotomy and a cervical incision, using the meticulous dissection described.

The prognosis of acute polyradiculoneuritis

IN PATIENTS with acute polyradiculoneuritis, cerebrospinal fluid pleocytosis,l profound sensory loss,2 papilledema,3 or progression for more than a few weeks2 has been said to be associated with incomplete recovery or recurrent disease. By exclusion of those with one or more of these “atypical” features, it has been thought possible to define a group with uniformly complete recovery. It has been suggested that the eponym, Guillain-Bar& syndrome, be applied only to this latter group.2 Evidence against the predictive value of such a classification has been provided by Forster and co-workers,4 who could find no correlation between cerebrospinal fluid formula and prognosis, and Duvoisin,b who could not relate rapidity of onset of symptoms to extent of recovery. Insdicient data are presently available on the long-term course of patients with this syndrome to permit resolution of these opposing points of view. We have accordingly reexamined 49 patients an average of eleven years after onset of symptoms.

Electrophysiologic Correlates of Peripheral Nervous System Maturation in Infancy and Childhood

Peripheral nervous system maturation in infancy and childhood varies with age, especially during the first 2 years of life. Electrophysiologic values therefore change significantly between different age groups within these first 2 years and are different from adult values. Normal values of motor and sensory nerve conduction, distal motor latency, F-wave latency, and evoked response amplitude of peripheral nerves commonly tested are reported in 155 healthy children in seven age groups from 1 week to 14 years. Interval changes are clearly shown, and in comparison with adult values, the whole group has significantly slower nerve conduction velocities, with reduced muscle and nerve evoked response amplitudes. These differences are important to recognize when evaluating the peripheral nervous system of children. (J Child Neurol 1993;8:336-338).