Multiple averaged records to identify Aδ-fibers in sensory nerves.

BACKGROUND: Existing methods identify only ≈10 Aδ-fibers in human sensory nerves per recording. This study examines methods to increase the detection of Aδ-fibers. NEW METHOD: Two to 20 averages of 500 replicate responses to epidermal nerve stimulation are obtained. Pairs of different averages are constructed. Each pair is analyzed with algorithms applied to amplitude and frequency to detect replication of responses to stimulation as "simultaneous similarities in two averages" (SS2AVs) at ≥99.5th percentile of control. In a pair of averages the latencies of amplitude and frequency SS2AVs for the same response to stimulation may differ by ≤0.25 ms. Therefore, Aδ-fibers are identified by the 0.25 ms moving sum of SS2AV latencies of the pairs of averages. RESULTS: Increasing averages increases pairs of different averages and detection of Aδ-fibers: from 2 to 10 Aδ-fibers with two averages (one pair) to >50 Aδ-fibers with 12-20 averages (66-190 pairs). COMPARISON WITH EXISTING METHOD(S): Existing methods identify ≤10 Aδ-fibers in 10 averages/45 pairs with the medians of amplitude and frequency algorithms applied to all 45 pairs. This study identifies Aδ-fibers (i) by applying these algorithms at the 99.5th percentile of control, (ii) to each pair of averages and (iii) by the 0.25 ms sum of algorithm identified events (SS2AVs) in all pairs. These three changes significantly increase the detection of Aδ-fibers, e.g., in 10 averages/45pairs from 10 to 45. CONCLUSIONS: Three modifications of existing methods can increase the detection of Aδ-fibers to an amount suitable (>50 with ≥12 averages) for statistical comparison of different nerves.

Median amplitude and frequency analysis of sensory nerve responses to intraepidermal stimulation.

BACKGROUND: In clinical practice, small myelinated sensory fibers conveying pain and other sensations, Aδ-fibers, cannot be examined with available nerve conduction study techniques. NEW METHOD: Equipment available in clinical neurophysiology laboratories is used to record from human sensory nerves multiple averaged responses to non-painful stimulation of intraepidermal nerves. Ten averaged responses are analyzed in all possible pair combinations with an algorithm applied to a 0.45 ms period of amplitude and frequency (power spectrum). The median of the algorithms is compared to control data to identify potentials generated as response to intraepidermal stimulation. RESULTS: Median analysis of the algorithm applied to amplitude and frequency of multiple record pairs identifies potentials with conduction velocities of Aδ-fibers. The analysis of frequency (power spectrum) adds data to the analysis of amplitude. Median analysis of multiple record pairs yields more data than analysis of one pair of alternate averages with the same algorithms. COMPARISON WITH EXISTING METHOD(S): At present, analysis of one pair of alternate average records with an algorithm is the only method to identify Aδ-fiber generated potentials. Median analysis of the same algorithm applied to the amplitude of multiple record pairs increases the number of Aδ-fiber generated potentials identified. Neither median analysis of amplitude nor frequency of multiple records pairs has ever been used for conduction studies of nerve fibers, including Aδ-fibers. CONCLUSIONS: Stimulation, recording and data analysis methods used in this study can be applied in the clinical EMG laboratory to identify the conduction velocities of Aδ-fibers in human sensory nerves.

Slowly conducting potentials in human sensory nerves.

BACKGROUND: In clinical practice, small myelinated sensory fibers, Aδ-fibers, conveying mainly pain and temperature sensations, cannot be examined with available nerve conduction study techniques. Currently, these fibers can only be examined with experimental or very specialized and not commonly available nerve conduction techniques, or only indirectly with cerebral evoked potentials. NEW METHOD: This study uses equipment and methods available in clinical neurophysiology laboratories to record from human sensory nerves ≥1000 averaged responses to focal, non-painful stimuli applied by a special electrode to epidermal nerves. The averaged responses to odd numbered stimuli are compared to the averaged responses to even numbered stimuli. An algorithm identifies potentials common in both averages. The 99th and 99.9th percentiles for this algorithm are obtained from control records without stimulation and applied to records with stimulation to identify potentials resulting from stimulation of intraepidermal nerves. RESULTS: The algorithm identifies numerous negative and positive potentials as being different from controls at the 99th and 99.9th percentile levels. The conduction velocities of the potentials range from of 1.3-29.9 m/s and are compatible with conduction velocities of Aδ-fibers. COMPARISON WITH EXISTING METHOD(S): No existing methods. CONCLUSIONS: The stimulation, recording and data analysis methods used in this study can be applied in the clinical EMG laboratory to identify Aδ-fibers in human sensory nerves.

Gastric mucosal nerve density: a biomarker for diabetic autonomic neuropathy?

BACKGROUND: Autonomic neuropathy is a frequent diagnosis for the gastrointestinal symptoms or postural hypotension experienced by patients with longstanding diabetes. However, neuropathologic evidence to substantiate the diagnosis is limited. We hypothesized that quantification of nerves in gastric mucosa would confirm the presence of autonomic neuropathy. METHODS: Mucosal biopsies from the stomach antrum and fundus were obtained during endoscopy from 15 healthy controls and 13 type 1 diabetic candidates for pancreas transplantation who had secondary diabetic complications affecting the eyes, kidneys, and nerves, including a diagnosis of gastroparesis. Neurologic status was evaluated by neurologic examination, nerve conduction studies, and skin biopsy. Biopsies were processed to quantify gastric mucosal nerves and epidermal nerves. RESULTS: Gastric mucosal nerves from diabetic subjects had reduced density and abnormal morphology compared to control subjects (p < 0.05). The horizontal and vertical meshwork pattern of nerve fibers that normally extends from the base of gastric glands to the basal lamina underlying the epithelial surface was deficient in diabetic subjects. Eleven of the 13 diabetic patients had residual food in the stomach after overnight fasting. Neurologic abnormalities on clinical examination were found in 12 of 13 diabetic subjects and nerve conduction studies were abnormal in all patients. The epidermal nerve fiber density was deficient in skin biopsies from diabetic subjects. CONCLUSIONS: In this observational study, gastric mucosal nerves were abnormal in patients with type 1 diabetes with secondary complications and clinical evidence of gastroparesis. Gastric mucosal biopsy is a safe, practical method for histologic diagnosis of gastric autonomic neuropathy.

Morphological features of nerves in skin biopsies.

Skin biopsy is an effective test for diagnosis of peripheral nerve disorders. The most commonly reported indication of abnormality in a skin biopsy is reduction of epidermal nerve density. Morphological changes of epidermal nerves and the underlying subepidermal nerve plexus provide added evidence for the presence of neuropathy. We determined the prevalence of epidermal axon swellings, dermal axon swellings, and a unique type of epidermal nerve that we call a crawler, in a group of normal subjects, diabetic subjects, and patients with idiopathic small fiber neuropathy. Other morphologic features examined include thinning of the subepidermal nerve plexus, sprouts at nerve terminals, encapsulated endings, and immunoreactive basal cells.

Late occurrence of chronic immune-mediated axonal polyneuropathy following bone marrow transplant for juvenile-onset alpha-mannosidosis.

A 23-year-old woman with juvenile-onset alpha-mannosidosis developed an axonal polyneuropathy more than a year following successful unrelated donor (URD) BMT complicated by chronic graft-versus-host disease (GVHD). Progressive muscle weakness and paresthesias developed over at least 4 months, and made her nonambulatory. Nerve conduction and EMG studies demonstrated an axonal sensorimotor neuropathy. Cerebral spinal fluid (CSF) IgG was elevated with two peaks not identified in serum. Strength improved after a single course of plasma exchange and continued to improve over 12 months. The response to plasma exchange, elevated CSF IgG production, and evidence of a serum IgM peak suggest an immune-mediated mechanism. Chronic polyneuropathies following BMT are rare and are usually temporally related to GVHD or infection. This patient's disease was unusual because of its late occurrence and chronic onset in the face of resolved GVHD and in the absence of infection.

Use of skin biopsy and skin blister in neurologic practice.

Recently developed immunohistochemical methods permit the visualization of intraepiderma! nerve fibers (ENFs) in punch skin biopsies and skin blisters. ENF density has been shown to be diminished in diabetic neuropathy as well as other focal and generalized sensory-predominant neuropathies, including the neuropathy associated with anti-retroviral therapy, idiopathic small-fiber sensory neuropathy, Fabry disease, and diabetic truncal radiculopathy. ENF depletion is often found prior to the development of clinical or eleo trodiagnostic abnormalities, making this procedure arguably the most sensitive diagnostic test for sensory neuropathies, particularly those with predominant involvement of unmyelinated fibers. Characteristic morphologic changes of epidermal nerves and the subepidermal neural plexus are often seen in these conditions as well. The fibers visualized by this technique are thought to be polymodal heat and mechanical nociceptors. We review the history, clinical applications, and methodology of this exciting technique.

Functional improvement of elderly residents of institutions.

Studies have shown that some elderly persons who suffer decline in activities of daily living (ADL) functioning experience an improvement. This phenomenon has been examined mainly among elderly persons in the community using summary ADL indices. This article examines functional improvement among 2,527 residents of institutions for semi-independent and frail elders in Israel in four specific ADLs--bathing, eating, bladder continence, and mobility--at two points in time, 2 to 4 years apart. Demographic, functional, and institutional variables were used to predict functional improvement through logistic regression. The variables were found to differentially affect each ADL, highlighting two opposite aspects of institutionalization--deterioration, on the one hand, and rehabilitation through intervention by highly trained staff, on the other.

Institutions for the elderly operating without a license: quality of care and the surveillance process.

In 1992, Israel's Services for the Aged identified private institutions for the elderly operating illegally, which are notorious for poor quality. This article presents the findings of screening visits in 97 "pirate" institutions, as part of a plan to improve surveillance, and evaluates the outcomes as a measure of the effectiveness of intervention. Although a high proportion of deficiencies was found, some institutions showed a significant ability to correct them.

Mononeuropathy multiplex due to infiltration of lymphoma in hematologic remission.

We report a case of progressive mononeuropathy multiplex in a patient with lymphoma in hematologic remission. At the time of presentation there was no evidence of meningeal or central nervous system metastasis. At autopsy, extensive infiltration of tumor cells was found in both femoral nerves. We review the literature pertaining to multifocal malignant lymphoid infiltration of peripheral nerves, which can occur during hematologic remission or in the absence of any evidence of systemic lymphoma.

Two-unit reliability analysis of questionnaires used in a regulatory system.

An interjudge reliability test was conducted to evaluate the questionnaires used in the surveillance of residential care institutions. Because the reliability test was carried out as part of the routine surveillance program and not as part of a controlled experiment, it was subject to deviations from the optimal reliability test model. However, this nonpure design provided an opportunity to not only examine the reliability of the items in the surveillance tool, but also to gain a better understanding of the use of a reliability test in an "imperfect" field setting. Two different surveyor teams administered the 257 questions on the questionnaires to a representative sample of 32 institutions on two separate occasions. In order to explain the variance in the reliability scores, a multivariate analysis was conducted for two units of analysis: the surveillance questions and the institutions. Based on the results of the reliability test, changes were introduced to improve the questionnaires and their administration.

Licensing, quality of care and the surveillance process.

As part of the evaluation of an experimental programme of surveillance of institutions for the semi-independent and frail elderly using the regulation, assessment, follow-up (RAF) method, an examination was made of the licensing status, quality of care, and completeness of the surveillance process. Included in the examination were 126 institutions which underwent the surveillance process between 1990 and 1993. Aims to investigate whether the RAF method of surveillance was being implemented in a professional and uniform manner. Concludes that surveyor's recommendations to grant or not grant a licence were usually based on findings about the quality of care. Nevertheless, in order to reinforce the relationship between licensing and quality of care, it was suggested that surveyors be given clear criteria of quality on which to base their recommendations regarding conditional licensing. It was found that the surveillance process is indeed implemented uniformly in long-term care institutions of varying quality.

Characteristics of motor unit discharge in subjects with hemiparesis.

We studied the discharge rates and recruitment characteristics of single motor units in paretic and contralateral arm muscles of 6 hemiparetic subjects. Motor unit activity in biceps brachii was recorded at different elbow torques, and the activity related both to the mean level of surface electromyographic activity, and to the degree of weakness. In 3 of the 6 subjects, there were significant reductions in mean discharge rate of motor units in the paretic muscle. All 6 subjects showed compression of the range of motoneuron recruitment forces, and a failure to increase motor unit discharge rate during voluntary force increases in paretic muscles. These rate reductions could potentially alter the precise match of motoneuron properties to the mechanical properties of the innervated muscle fibers, and reduce the efficiency of muscle contraction. This reduction could lead, in turn to increased effort, to fatigue, and ultimately to a sense of weakness for voluntary force generation.

Improving regulation of care.

The JDC-Brookdale Institute of Gerontology, in collaboration with Israel's Ministry of Labor and Social Affairs and Ministry of Health, has developed a program to improve government regulation of long-term care institutions for the elderly, and thus the quality of institutional care. The aim of the program was to introduce greater uniformity and objectivity into the existing surveillance system, increase the participation of institution residents, and ensure public access to instruments and criteria. The tracer methodology was used and tracers representing the medical, nursing, psychosocial and environmental-operational areas were developed in consultation with specialists in each field. The program was welcomed by surveillance personnel, and implemented on a nation-wide basis. Although there have been difficulties with its implementation, these have largely been resolved through discussion, workshops and supplementary training for surveyors. Due to the program's success, new programs are being developed to improve the regulation of other kinds of institution.

Intermittent encephalopathy, reversible nerve conduction slowing, and MRI evidence of cerebral white matter disease in methylenetetrahydrofolate reductase deficiency.

We describe a patient with methylenetetrahydrofolate reductase (MTHFR) deficiency in whom clinical and electrophysiologic fluctuations paralleled exacerbations of hyperhomocyst(e)inemia. MRI demonstrated abnormalities characteristic of a leukodystrophy.

Effects of cutaneous stimulation on ipsilateral and contralateral motoneuron excitability: an analysis using H reflexes and F waves.

F waves are altered by conditioning stimulation of digital nerves. We investigated this by studying series of median nerve F waves recorded from abductor pollicis brevis (APB) 20, 50, 80, 100, 150, 200, and 500 milliseconds (ms) after conditioning stimuli applied to the ipsilateral or contralateral second digit in six normal subjects. The persistence and mean amplitude of the F waves were determined at each delay and compared with control F waves without conditioning stimuli. Ipsilateral afferent stimulation produced inhibition of F wave amplitude and persistence when applied 50 to 100 ms before the test stimulus, while contralateral conditioning stimuli facilitated the F wave when applied 80 to 200 ms before the test stimulus. Similar results were obtained in H reflex studies in one neurologically normal subject with a reproducible H reflex recording from the APB. These findings illustrate definable ipsilateral and contralateral postsynaptic influences of afferent fibers on motoneuron excitability in the arms.