Neil R. Holland

Intraepidermal nerve fiber density in patients with painful sensory neuropathy

Article abstract-Despite prominent symptoms of neuropathic pain, patients with small-fiber sensory neuropathies have few objective abnormalities on clinical examination and routine electrodiagnostic studies. We quantified intraepidermal nerve fiber (IENF) density in sections of skin obtained by punch skin biopsy, and found it to be significantly reduced in patients with painful sensory neuropathies compared with age-matched control subjects. In addition, IENF density correlated with clinical estimates of neuropathy severity, as judged by the extent of clinically identifiable sensory abnormalities. IENF density at the calf was lower than that obtained from skin at more proximal sites, indicating the length dependency of small-fiber loss in these neuropathies. NEUROLOGY 1997;48: 708-711

Epidermal innervation: changes with aging, topographic location, and in sensory neuropathy.

In previous work we demonstrated little effect of aging on the density and spatial pattern of epidermal innervation, however, this was restricted to two sites proximal and distal in the leg. To expand on these observations, we used punch skin biopsy in ten healthy controls to examine the variation in intra-epidermal nerve fiber (IENF) density at multiple specific sites in the leg. There was a consistent gradient in IENF from proximal to distal sites in all subjects, but minimal effect of age was noted. In the older age group (> or =70 years), the IENF densities ranged from 28.6+/-1.9 IENF/mm at the trunk to 15.5+/-1.5 at the distal leg. In a group of six patients with painful sensory neuropathy, we confirmed a length-dependent reduction in IENF. We observed what may be a predegenerative change, namely increased branching of epidermal nerve fibers at clinically unaffected sites. These data suggest little age-related change in IENF, at least up to age 75 years, in healthy normals. The increased branching complexity noted in unaffected sites in patients with sensory neuropathies implies that this may be a predegenerative change, preceding the actual loss of nerve fibers. Skin biopsy may be a useful tool for assessing the topographic extent and degree of nerve fiber damage in sensory neuropathies and its quantitative interpretation should be little affected by aging changes.

Cytomegalovirus encephalitis in acquired immunodeficiency syndrome (AIDS)

Cytomegalovirus encephalitis (CMVE) is frequently diagnosed only at postmortem because its specific clinical features have not been fully identified. We have described the clinical, radiologic, and laboratory features of CMVE in a retrospective review of 14 autopsy-confirmed cases of CMVE and compared them with a control group of demented acquired immunodeficiency syndrome (AIDS) patients without CMVE. CMVE was more common among homosexual men, and a subacute onset was more typical (mean duration of presenting symptoms was 3.5 weeks versus 18 weeks in demented controls). Median survival times were 4.6 weeks for CMVE and 28 weeks for controls. CMVE was accompanied by prominent systemic CMV infection at autopsy, including CMV adrenalitis (92%), CMV pneumonitis (42%), systemic Mycobacterium avium intracellulare (MAI; 58%), and CMV retinitis (58%). Hyponatremia and MAI bacteremia were found in 58% of CMVE cases. Polymerase chain reaction (PCR) of CSF samples identified CMV genome in 33% of CMVE cases. CMVE was associated with periventricular enhancement on CTs and periventricular lesions with meningeal enhancement on MRI scans. CMVE should be particularly suspected in homosexual men presenting with subacute encephalopathy who have had AIDS for more than 1 year and have a history of systemic CMV infection. Other features supporting the diagnosis of CMVE include periventricular lesions, hyponatremia, and identification of CMV genome in CSF by PCR.

CNS demyelination associated with copper deficiency and hyperzincemia.

CNS demyelination is not a previously reported feature of acquired copper deficiency. The authors report two patients with idiopathic hypocupremia and hyperzincemia, hematologic changes of copper deficiency, and extensive CNS demyelination. Hematologic recovery followed copper supplementation, both initially and after relapse off copper therapy, while serum zinc levels remained high and the neurologic abnormalities only stabilized.

Higher electrical stimulus intensities are required to activate chronically compressed nerve roots: Implications for intraoperative electromyographic pedicle screw testing

Study Design. A comparison of the electrical thresholds required to evoke myogenic responses from direct stimulation of normal and chronically compressed nerve roots. Objective. To determine whether intraoperative electromyographic testing to confirm the integrity of instrumented pedicles should be performed at higher stimulus intensities in cases where there is preoperative lumbosacral radiculopathy. Summary of Background Data. Postoperative neurologic deficits may occur as a result of pedicle screw misplacement during spinal instrumentation. The failure to evoke myogenic responses from stimulation of pedicle holes and screws at intensities of 6‐8 mA is commonly used to exclude bony pedicular wall perforation. Methods. Direct nerve root stimulation was used to compare the stimulus thresholds of normal and compressed nerve roots in six patients with limb weakness from chronic lumbosacral radiculopathy. Results. The stimulus thresholds of chronically compressed nerve roots significantly exceeded those of normal nerve roots, indicating partial axonal loss (axonotmesis). In most cases, the direct stimulus thresholds of compressed nerve roots exceeded 10 mA. Conclusions. When instrumentation is placed at spinal levels where there is preexisting chronic lumbosacral radiculopathy, holes and screws may need to be stimulated at higher intensities to exclude pedicular perforation and prevent further iatrogenic nerve root injury.

Continuous electromyographic monitoring to detect nerve root injury during thoracolumbar scoliosis surgery

Study Design. The results of intraoperative monitoring during a case of nerve root injury sustained from scoliosis surgery to the thoracolumbar spine are described. Objectives. To improve the efficacy of intraoperative monitoring in preventing nerve root injury during scoliosis surgery. Summary of Background Data. Posterior tibial nerve somatosensory‐evoked potentials are the electrophysiologic modality most commonly used for spinal cord monitoring during thoracolumbar spine surgery. Although radiculopathy is a more frequent postoperative complication than myelopathy, monitoring of mixed‐nerve, somatosensory‐evoked potentials may not detect injuries to individual nerve roots. Methods. The patient described in this report developed left L5 radiculopathy after scoliosis surgery to the thoracolumbar spine. During surgery, intraoperative electromyographic monitoring identified frequent trains of neurotonic discharges in the left anterior tibial muscle. Bilateral, posterior, tibial nerve, somatosensory‐evoked potentials remained normal. The left L5 nerve root was explored 9 days after the original surgery and was found to be compressed by bony structures. Electrophysiologic testing showed that the nerve root had undergone significant Wallerian degeneration, but remained in partial continuity. Results. Nerve root injury was detected by neurotonic discharges identified during intraoperative electromyographic monitoring, but not by somatosensory‐evoked potentials, which remained normal. When the injured nerve root was explored, a simple electromyographic technique was used to characterize the extent and type of injury. Conclusions. The authors of this study recommend electromyographic monitoring of appropriate lumbosacral myotomes in addition to somatosensory‐evoked potentials during this type of procedure.

Relapsing hypocupraemic myelopathy requiring high-dose oral copper replacement

Adult-onset copper deficiency with neurological manifestations is a newly recognised syndrome. Long-term oral copper replacement therapy has been the mainstay of treatment in the literature. A case of relapsing hypocupraemic myelopathy responsive to increased doses of copper replacement is reported. Standard doses of copper may not be sufficient for all patients.

CNS demyelination from zinc toxicity

A 45-year-old man presented with a 4-month history of progressive fatigue, lethargy, shortness of breath on exercise, and generalized numbness with paresthesias. Initial bloodwork showed severe pancytopenia, with a hemoglobin of 4.9 g/dL, a white blood cell count of 1,000 mm−3, and a platelet count of 121,000 mm−3. Bone marrow biopsy showed aplastic anemia with ringed sideroblasts. This was subsequently attributed to zinc toxicity with associated copper deficiency. His serum zinc level was 192 μg/dL (normal, 70 to 150 μg/dL), his serum copper level was 0 μg/dL (normal, 70 to 155 μg/dL), and his serum ceruloplasmin level was 6.8 mg/dL (normal, 16.2 to 35.6 mg/dL). Blood levels of other heavy metals, including lead, mercury, and arsenic, were normal. He was transfused with 4 …

Intraoperative electrodiagnostic testing during cross-chest C7 nerve root transfer

Trauma to the brachial plexus may cause avulsion of cervical roots from the spinal cord, stretch injury to the neural elements of the plexus, or both. Identification of patients with root avulsions is crucial, as nerve grafting onto such roots cannot be expected to result in return of function. Preoperative electromyography is often helpful in this regard, but diagnosis is more difficult with combination injuries, particularly when individual roots are differentially affected. Even finding obvious macroscopic evidence of injury to the brachial plexus elements at the time of surgical exploration does not exclude coexisting occult root avulsions. Root avulsion is only definitively excluded if direct stimulation of the individual surgically exposed cervical nerve root elicits reproducible cortical somatosensory evoked potentials (SEPs). With total brachial plexus root avulsions, only the phrenic, spinal accessory, cervical plexus, and intercostal nerves remain centrally connected and available for nerve transfer. Because the number of nerve fibers available for grafting from these sources is frequently insufficient to restore adequate function, the recently reported use of cross-chest C7 root nerve transfer and grafting for brachial plexus avulsion is of particular interest. The purpose of this article is to describe the intraoperative electrodiagnostic testing that should be performed before undertaking such a procedure, in order to minimize potentially devastating complications. CASE REPORT

A case of CNS cryptococcosis presenting with slowly alternating skew deviation

Alternating skew deviation is a rare malfunction of vertical ocular motility, which has previously been described with lesions of the brainstem and cerebellum, although the precise localization is unknown. We describe an HIV seronegative patient with CNS cryptococcosis, whose initial presentation included slowly alternating skew deviation.