Hereditary neuropathy with liability to pressure palsy: fulminant development with axonal loss during military training.

Hereditary neuropathy with liability to pressure palsy (HNPP) is characterised by recurrent mononeuropathies following minor trauma. We describe a case of fulminant HNPP beginning on the first day of military physical training. Protracted weakness, muscle atrophy, hand contractures, and multifocal sensory loss developed during a further three weeks of basic training. Nerve conduction changes were typical of HNPP, but without segmental slowing. Electromyographically, there was prominent acute denervation in muscles of the hands and right shoulder. Sural nerve biopsy demonstrated tomaculae and remyelination. Genetic testing revealed PMP-22 gene deletion. This case report demonstrates that HNPP can present with rapidly progressive peripheral nerve dysfunction and electrophysiological evidence of focal axonal loss.

Early stroke treatment associated with better outcome: the NINDS rt-PA stroke study.

BACKGROUND: The National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study showed a similar percentage of intracranial hemorrhage and good outcome in patients 3 months after stroke treatment given 0 to 90 minutes and 91 to 180 minutes after stroke onset. At 24 hours after stroke onset more patients treated 0 to 90 compared to 91 to 180 minutes after stroke onset had improved by four or more points on the NIH Stroke Scale (NIHSS). The authors performed further analyses to characterize the relationship of onset-to-treatment time (OTT) to outcome at 3 months, early improvement at 24 hours, and intracranial hemorrhage within 36 hours. METHODS: Univariate analyses identified potentially confounding variables associated with OTT that could mask an OTT-treatment interaction. Tests for OTT-treatment interactions adjusting for potential masking confounders were performed. An OTT-treatment interaction was considered significant if p < or = 0.10, implying that treatment effectiveness was related to OTT. RESULTS: For 24-hour improvement, there were no masking confounders identified and there was an OTT-treatment interaction (p = 0.08). For 3-month favorable outcome, the NIHSS met criteria for a masking confounder. After adjusting for NIHSS as a covariate, an OTT-treatment interaction was detected (p = 0.09): the adjusted OR (95% CI) for a favorable 3-month outcome associated with recombinant tissue-type plasminogen activator (rt-PA) was 2.11 (1.33 to 3.35) in the 0 to 90 minute stratum and 1.69 (1.09 to 2.62) in the 91 to 180 minute stratum. In the group treated with rt-PA, after adjusting for baseline NIHSS, an effect of OTT on the occurrence of intracranial hemorrhage was not detected. CONCLUSIONS: If the NINDS rt-PA Stroke Trial treatment protocol is followed, this analysis suggests that patients treated 0 to 90 minutes from stroke onset with rt-PA have an increased odds of improvement at 24 hours and favorable 3-month outcome compared to patients treated later than 90 minutes. No effect of OTT on intracranial hemorrhage was detected within the group treated with rt-PA, possibly due to low power.

Venipuncture-induced causalgia: anatomic relations of upper extremity superficial veins and nerves, and clinical considerations.

BACKGROUND: In 1994, 11 patients with injury to upper extremity cutaneous nerves after routine venipuncture were reported. All developed causalgia (Complex Regional Pain Syndrome, Type 2). Nerve injury appeared secondary to direct trauma via "inappropriate" needle or bolused material entry into the plane of the nerves beneath the veins, or nerves overlying the veins. However, in 3 of 13 additional patients, the venipunctures were properly performed and atraumatic. STUDY DESIGN AND METHODS: To explore the anatomic relationships of superficial veins and cutaneous nerves with regard to the role of direct nerve trauma during venipuncture in the development of causalgia, the 14 upper extremities of seven randomly chosen cadavers were dissected at three common venipuncture sites. In addition, the clinical features of all 24 patients are presented. RESULTS: Major branches of cutaneous nerves were superficial to and overlay veins in six extremities. In multiple instances, nerves and veins were intertwined, requiring detailed dissection to separate them. In the classic situation, nerves were immediately as deep as veins, often with no fascial separation. CONCLUSIONS: Anatomical relationships between upper extremity superficial veins and cutaneous nerves are so intimate that needle-nerve contact during venipuncture is common. Because venipuncture-induced nerve injuries are rare, factors other than direct nerve contact appear necessary for the chronic pain syndrome to occur.

Linkage of hereditary distal myopathy with desmin accumulation to 2q.

We are investigating the genetics of a large family with an autosomal dominant form of hereditary distal myopathy. This slowly progressive myopathy begins during early adulthood in the distal leg muscles, producing a gait disturbance. Cardiomyopathy is also present in most affected family members, manifesting itself as conduction block or congestive heart failure. Histologically, an accumulation of the protein, desmin, occurs in the subsarcolemmal spaces of myofibers. We have performed linkage analyses of this family, and have mapped the location of the gene causing the myopathy to human chromosome 2q33. The gene is within a 17-cM segment of chromosome 2q bounded by the DNA markers D2S2248 and D2S401. The best candidate gene for this myopathy is desmin.

A missense mutation in the desmin rod domain is associated with autosomal dominant distal myopathy, and exerts a dominant negative effect on filament formation.

In some myopathies of distal onset, the intermediate filament desmin is abnormally accumulated in skeletal and cardiac muscle. We report the first point mutation in desmin cosegregating with an autosomal dominant form of desmin-related myopathy. The L345P desmin missense mutation occurs in a large, six generation Ashkenazi Jewish family. The mutation is located in an evolutionarily highly conserved position of the desmin coiled-coil rod domain important for dimer formation. L345P desmin is incapable of forming filamentous networks in transfected HeLa and SW13 cells. We conclude that the L345P desmin missense mutation causes myopathy by interfering in a dominant-negative manner with the dimerization-polymerization process of intermediate filament assembly.

A multi-modality assessment of peripheral nerve function in organophosphate-pesticide applicators.

Health effects from chronic, low-level exposure to organophosphate pesticides have not been studied extensively and are not well-established. This report follows up a study in New York State in which a cohort of 90 male pesticide applicators were found to have increased vibration sensitivity thresholds, compared with a matched sample drawn from the general population. This investigation examined the nature and extent of peripheral nerve abnormalities in a small subgroup of the original cohort. Of the nine subjects studied, four had clinical evidence of peripheral neuropathic dysfunction, and one who was normal physiologically showed electrophysiological abnormalities. The remaining four showed no clinical, electrophysiologic, or quantitative signs or other abnormalities. This study adds to the growing evidence that organophosphates are toxic to the peripheral nervous system at levels of exposure that do not induce acute or subacute symptomatology.

American Association of Electrodiagnostic Medicine guidelines for outcome studies in electrodiagnostic medicine.

Based on a review of the literature and the clinical research experience of the authors and reviewers, the AAEM proposes 17 criteria which should be used to construct and evaluate diagnostic and/or therapeutic outcome studies for patients with symptoms and signs of neuromuscular diseases. Neuromuscular diseases are defined as diseases that cause pathology and/or dysfunction of the sensory, motor, and/or autonomic nerve offers and/or muscles.

Peripheral nerve injury and causalgia secondary to routine venipuncture.

I examined 11 patients with upper-extremity causalgia secondary to peripheral nerve injury occurring during routine venipuncture. The nerves affected were the medial (n = 5) and lateral (n = 2) antebrachial cutaneous in the antecubital fossa, the superficial radial at the wrist (n = 2), and the dorsal sensory branches in the hand (n = 2). Anatomically, nerves lie on a plane just beneath and in close proximity to veins, making them vulnerable to injury during the procedure.

Autosomal dominant distal myopathy with desmin storage: a clinicopathologic and electrophysiologic study of a large kinship.

A large family is described with an autosomal dominant distal myopathy, the nature of which prompts the reevaluation of current classifications of these disorders. The disease begins in early to middle adulthood with gait disturbance due to distal leg weakness, and progresses over 5-10 years to involve all extremities, as well as bulbar, respiratory, and facial muscles. There is frequent cardiac involvement, manifest by arrhythmias, conduction blocks, and congestive failure, resulting in premature demise. On electromyography there is prominent spontaneous activity, short duration motor unit potentials, and polyphasia. Muscle biopsies from multiple family members at different stages of the disease are characterized by desmin storage and autophagocytosis. This distal myopathy differs from other phenotypically similar disorders in its rapidity of progression, fatal course and pathologic features. The role and specificity of excessive desmin accumulation in this and other myopathic and cardiac disorders are unknown.

Diabetic neuropathy.

The neuropathy associated with diabetes mellitus is arguably the most common peripheral neuropathy in the developed world. It can be classified into symmetrical and asymmetrical forms. The symmetrical form is predominantly sensory and autonomic, whereas the asymmetrical form can be sensory, or motor, or both, and can affect individual cranial or peripheral nerves. Pathologic and electrophysiologic studies indicate that the symmetrical polyneuropathy is characterized by a distally accentuated loss of myelinated and unmyelinated axons. The multifocal nature of the axonal degeneration and its association with vascular disease in the same pathologic specimens strongly suggest an ischemic cause involving the endoneurial microvascular circulation. The underlying biochemical abnormality appears to be the production of advanced glycosylated end products (AGEPs), in the presence of chronic hyperglycemia, which accumulate on endothelial proteins, causing basement membrane thickening and endothelial cell change. This produces multifocal vascular disease that, in turn, reduces nerve blood flow, causing endoneurial hypoxia and generating oxygen free radicals. Multifocal ischemic neuronal damage results. Currently, there is no accepted treatment, although long-term control of hyperglycemia is beneficial. Symptomatic relief of the burning pain is the most vexing therapeutic problem; tricyclic antidepressants and anticonvulsants have been used alone and together with varying success.

Clinical-radiographic correlations within the first five hours of cerebral infarction.

Fifty patients, ages 54-79, with ischemic hemispheric strokes productive of hemiparesis, at a minimum, underwent standardized neurological evaluations, computed tomographic scanning and cerebral angiography (N = 38) or carotid ultrasound (N = 12) within 5 h of onset. A second scan was performed at 5-7 days. Clinical scores were not associated with a history of, or the presence of: hypertension, smoking or cardiac disease, including atrial fibrillation, nor with severe internal carotid artery stenosis or occlusion. Clinical scores were adversely affected by early scan abnormalities (especially mass effect), lesion size, intracranial arterial occlusions, elevated serum glucose levels and the subsequent development of hemorrhagic infarction. Glucose levels correlated with infarct size and the development of hemorrhagic infarction. Delayed intracranial arterial filling and collateral flow were associated with reduced infarct size but did not confer clinical protection. We believe that combining the initial glucose level and scan results has prognostic significance, and early angiography is valuable in characterizing infarct etiology and assessing clinical severity.

The influence of the stimulus on normal sural nerve conduction velocity: a study of the latency of activation.

Conduction along the sural nerve was studied in 64 normal subjects using near-nerve electrodes. Conduction velocities over the same nerve segments were calculated: (1) from the latency recorded from a site of stimulation to a site of recording (1R-method); and (2) from the difference in latency between 2 recording sites, the site of stimulation being situated elsewhere along the nerve (2R-method). Consistently faster velocities were seen with the 2R-method and could best be explained by a fixed delay of about 0.15 ms at the stimulus site (latency of activation, utilization time). This delay was markedly prolonged when a ramp rather than a rectangular stimulus was applied, though fast fibers were excited with both types of stimuli. The delay is thought to be dependent on the relationship between the density of current at the stimulus site and the threshold of responding fibers.

Conduction studies of the normal sural nerve.

The sural nerve was studied orthodromically using the near-nerve technique in 273 normal subjects (155 females, 118 males) aged 5 to 90 years. The sensory action potential (SAP), evoked at the dorsum of the foot, was recorded at the lateral malleolus and midcalf, and at the midcalf when evoked at the lateral malleolus. In addition, the SAP was recorded at intermediate distal sites and at proximal sites at the popliteal fossa, the gluteal fold, and the S-1 root. The amplitude of the SAP recorded at midcalf was 32% higher in females than in males. This was probably due to volume-conduction properties, as differences between genders were less noticeable at more distal recording sites. The amplitude decreased steeply and exponentially with age. Conduction distance had a strong influence on the amplitude of the SAP, which decreased with increasing distance following a power relationship with an exponent of 1.4 to 1.7. This decrease was due to temporal dispersion with decreased summation and increased phase cancellation. The conduction velocity was slightly lower along the very distal course of the nerve than along more proximal segments.

Computed tomographic-angiographic findings within the first five hours of cerebral infarction.

BACKGROUND AND PURPOSE: Modern management of acute stroke necessitates early diagnosis. To this end, we sought to delineate the radiographic features of focal hemispheric infarction within 5 hours of ictus. METHODS: Fifty patients, ages 54-79, with ischemic strokes productive of at least hemiparesis underwent computed tomographic scanning and cerebral angiography (n = 38) or carotid ultrasound (n = 12). Radiographic lesions were characterized for location, size, and pathophysiology. RESULTS: Acute abnormalities, hypodensity, and mass effect were seen in 56% of scans and confirmed on a second scan 5-7 days later. Intracranial angiographic abnormalities occurred in 61% of patients: arterial occlusions in 45% and delayed arterial filling in 16%. Hemorrhagic infarctions occurred in 26% of second scans and were associated with mass effect (100%) and arterial occlusions (89%). Infarcts with hemorrhagic transformation were larger on both scans than those without (p = 0.001). Of four patients with infarctions in watershed territories on the scans, two had middle cerebral artery occlusions on angiography, thereby questioning the specificity of such scan lesions to low-flow states. CONCLUSIONS: We conclude that cerebral infarctions are often visible on early scans, but their locations may not be etiologically determinative. The infarcts associated with intracranial arterial occlusions (45%) were of thromboembolic origin, but, given current controversies as to the pathophysiology of lacunar and watershed infarctions, we cannot ascertain the etiology in the remainder. These findings are relevant to the new stroke therapies that require administration in the first hours after infarction.

The idiopathic polyradiculoneuropathies: a historical guide to an understanding of the clinical syndromes.

Recognition of the idiopathic polyradiculoneuropathies began with Graves, Landry and Dumenil who, respectively, suggested, implied and established the peripheral nervous system as a site of disease. Over the ensuing decades other neurologists separated the idiopathic disorders from neuropathies of known cause, poliomyelitis and myelopathies. Guillain, Barré and Strohl described the acute benign syndrome and its cerebrospinal fluid abnormalities. Haymaker & Kernohan solidified the features of the acute disorder as did Dyck et al and Prineas & McLeod for the relapsing and chronic conditions. Currently the idiopathic polyradiculoneuropathies are regarded as autoimmune in nature, clinically generalized with some cases having focal involvement, and of varying severity with only occasional fatalities. Neurologists are divided as to whether the acute and chronic disorders represent 2 different conditions or whether they are 2 forms in the spectrum of a single disorder. This author favors the concept of a single disorder with multifarious manifestations.