Clinical and imaging characterization of progressive spastic dysarthria.

BACKGROUND AND PURPOSE: To describe speech, neurological and imaging characteristics of a series of patients presenting with progressive spastic dysarthria as the first and predominant sign of a presumed neurodegenerative disease. METHODS: Participants were 25 patients with spastic dysarthria as the only or predominant speech disorder. Clinical features, pattern of MRI volume loss on voxel-based morphometry and pattern of hypometabolism on F18-fluorodeoxyglucose positron emission tomography (FDG-PET) scan are described. RESULTS: All patients demonstrated speech characteristics consistent with spastic dysarthria, including strained voice quality, slow speaking rate, monopitch and monoloudness, and slow and regular speech alternating motion rates. Eight patients did not have additional neurological findings on examination. Pseudobulbar affect, upper motor neuron pattern limb weakness, spasticity, Hoffman sign and positive Babinski reflexes were noted in some of the remaining patients. Twenty-three patients had electromyographic assessment and none had diffuse motor neuron disease or met El Escorial criteria for amyotrophic lateral sclerosis. Voxel-based morphometry revealed striking bilateral white matter volume loss affecting the motor cortex (BA 4), including the frontoparietal operculum (BA 43) with extension into the middle cerebral peduncle. FDG-PET showed subtle hypometabolism affecting the premotor and motor cortices in some patients, particularly in those who had a disease duration longer than 2 years. CONCLUSIONS: A neurodegenerative disorder that begins focally with spastic dysarthria due to involvement of the motor and premotor cortex and descending corticospinal and corticobulbar pathways is characterized. The descriptive label 'progressive spastic dysarthria' to best capture the dominant presenting feature of the syndrome is proposed.

Cervical spine MR imaging findings of patients with Hirayama disease in North America: a multisite study.

BACKGROUND AND PURPOSE: Most studies of HD have been conducted in Asia, particularly Japan. To characterize the MR imaging findings of North American patients with HD, we reviewed neutral and flexion cervical MR imaging examinations performed for possible HD at 3 academic medical centers located in the Southeastern, Southwestern, and Midwestern regions of the United States. MATERIALS AND METHODS: Three neuroradiologists assessed the MR imaging examinations in a blinded fashion and reached a consensus rating for LOA of the posterior dura to the spine, lower spinal cord atrophy, spinal cord T2 hyperintensity, loss of cervical lordosis, anterior dural shift with flexion, and confidence of imaging diagnosis. Final reference diagnosis was established separately with a retrospective chart review by a neurologist. RESULTS: Twenty-one patients met the criteria for HD, all were North American males and all who reported their race were white. Seventeen patients did not meet the criteria and served as controls. Four imaging attributes, LOA, dural shift with flexion, consensus diagnosis of neutral images, and consensus diagnosis of combined neutral and flexion images were all able to discriminate the group with HD from the group without HD (P < .05 for each). Findings of HD were often present on neutral images, but the addition of flexion images increased diagnostic confidence. CONCLUSIONS: MR imaging findings in white North American patients with HD include LOA on neutral images and forward displacement of the dura with flexion. Findings are often present on neutral MR images and, in the appropriate clinical scenario, should prompt flexion MR imaging to evaluate anterior dural shift.

Predicting survival in frontotemporal dementia with motor neuron disease.

OBJECTIVE: To determine whether clinical and demographic features are associated with prognosis in patients with frontotemporal dementia and motor neuron disease (FTD-MND). METHODS: This was a case series of FTD-MND categorized according to behavioral- or language-dominant symptoms at presentation and throughout the disease course. Demographic, clinical, imaging, and survival data were analyzed with respect to dominant FTD-MND type. Voxel-based morphometry was used to assess and compare regional patterns of atrophy in behavioral- and language-dominant FTD-MND types. RESULTS: Of the 56 patients with FTD-MND who were identified, 31 had dominant behavioral symptoms and 25 had dominant language symptoms; 53 patients had died. A survival difference was present between types, with patients with behavioral-dominant symptoms surviving 506 days longer than patients with language-dominant symptoms (mean 1,397 vs 891 days; p = 0.002). There was also a difference in time from diagnosis to death (p = 0.02) between groups. Patients with language-dominant disease were more likely to have bulbar-onset than limb-onset motor neuron disease (MND) (p = 0.01). There was a similar pattern of frontal and temporal lobe atrophy in both types, although there was some evidence for the behavioral type to have more frontal atrophy and the language type to have more left temporal atrophy. CONCLUSIONS: In our series of patients with FTD-MND, language-dominant FTD-MND was associated with bulbar-onset MND and a shorter survival. There was also evidence that the dominant FTD-MND type is related to differences in brain atrophy patterns.

Clinically suspected fibrocartilaginous embolism: clinical characteristics, treatments, and outcomes.

OBJECTIVE: To study the frequency, demographics, clinical characteristics, and outcomes of patients with an antemortem diagnosis of fibrocartilaginous embolism (FCE), a rare cause of spinal cord and cerebral infarction because of the presumed embolization of nucleus pulposus material into the vascular circulation. METHODS: We retrospectively reviewed the institutional experience of patients who received an antemortem diagnosis of FCE by their treating physician at the Mayo Clinic (Rochester, MN, USA) from 1997 to 2009. All patients underwent laboratory, radiological, and clinical exclusion of other possible and related diagnoses. RESULTS: Of 164 patients with acute spinal cord infarction seen during the study timeframe, 9 (5.5%; 95% CI 2.5, 10.2%) met inclusion criteria for high likelihood of FCE (6 men, 3 women; median age 46 years old, range 21-64). All patients were severely affected (median modified Rankin Scale 4, median Barthel index 45; mean time to evaluation 57 days). One patient (1/9) experienced concomitant cerebral infarction. No patients had noticeable improvement from steroid treatment. CONCLUSION: The diagnosis of FCE in life is common at this referral center, accounting for 5.5% of all cases of acute spinal cord infarction seen. Although FCE is a postmortem diagnosis, we propose clinical criteria for FCE in life to better characterize the relatively high number of patients with unexplained ischaemic myelopathy.

Subcutaneous IGF-1 is not beneficial in 2-year ALS trial.

BACKGROUND: Previous human clinical trials of insulin-like growth factor type I (IGF-1) in amyotrophic lateral sclerosis (ALS) have been inconsistent. This phase III, randomized, double-blind, placebo-controlled study was undertaken to address whether IGF-1 benefited patients with ALS. METHODS: A total of 330 patients from 20 medical centers were randomized to receive 0.05 mg/kg body weight of human recombinant IGF-1 given subcutaneously twice daily or placebo for 2 years. The primary outcome measure was change in their manual muscle testing score. Secondary outcome measures included tracheostomy-free survival and rate of change in the revised ALS functional rating scale. Intention to treat analysis was used. RESULTS: There was no difference between treatment groups in the primary or secondary outcome measures after the 2-year treatment period. CONCLUSIONS: Insulin-like growth factor type I does not provide benefit for patients with amyotrophic lateral sclerosis.

Misdirection of regenerating motor axons after nerve injury and repair in the rat sciatic nerve model.

Misdirection of regenerating axons is one of the factors that can explain the poor results often found after nerve injury and repair. In this study, we quantified the degree of misdirection and the effect on recovery of function after different types of nerve injury and repair in the rat sciatic nerve model; crush injury, direct coaptation, and autograft repair. Sequential tracing with retrograde labeling of the peroneal nerve before and 8 weeks after nerve injury and repair was performed to quantify the accuracy of motor axon regeneration. Digital video analysis of ankle motion was used to investigate the recovery of function. In addition, serial compound action potential recordings and nerve and muscle morphometry were performed. In our study, accuracy of motor axon regeneration was found to be limited; only 71% (+/-4.9%) of the peroneal motoneurons were correctly directed 2 months after sciatic crush injury, 42% (+/-4.2%) after direct coaptation, and 25% (+/-6.6%) after autograft repair. Recovery of ankle motion was incomplete after all types of nerve injury and repair and demonstrated a disturbed balance of ankle plantar and dorsiflexion. The number of motoneurons from which axons had regenerated was not significantly different from normal. The number of myelinated axons was significantly increased distal to the site of injury. Misdirection of regenerating motor axons is a major factor in the poor recovery of nerves that innervate different muscles. The results of this study can be used as basis for developing new nerve repair techniques that may improve the accuracy of regeneration.

Regional anesthesia does not increase the risk of postoperative neuropathy in patients undergoing ulnar nerve transposition.

UNLABELLED: The use of regional anesthetic techniques in patients with preexisting neuropathies has been widely debated. The possibility of needle- or catheter-induced trauma, local anesthetic toxicity, or neural ischemia during regional blockade may place patients with underlying mechanical, ischemic, or metabolic neurologic derangements at increased risk of progressive neural injury. We evaluated the safety of regional versus general anesthesia in patients with a preexisting ulnar neuropathy undergoing ulnar nerve transposition. All patients (n = 360) who underwent ulnar nerve transposition at the Mayo Clinic from 1985 to 1999 were retrospectively studied. A general anesthetic was performed in 260 (72%) patients. The remaining 100 (28%) patients received an axillary block, including 64 patients in whom an ulnar paresthesia or nerve stimulator motor response was elicited at the time of block placement. Patient characteristics, the severity of preoperative ulnar nerve dysfunction, and surgical variables were similar between groups. Anesthetic technique did not affect neurologic outcome (new or worsening pain, paresthesias, numbness, or motor weakness) immediately after surgery or at 2 or 6 wk after surgery. All six patients in the Axillary Block group who reported new or worsening neurologic symptoms after surgery had received bupivacaine in combination with either an ulnar paresthesia or motor response. By using logistic regression, bupivacaine was identified as an independent risk factor for worsening of ulnar nerve function compared with other local anesthetics. We conclude that axillary blockade is a suitable anesthetic technique for this procedure. IMPLICATIONS: The use of regional anesthetic techniques in patients with preexisting neuropathies has been widely debated. Theoretical concerns include the risk of progressive nerve damage from direct needle trauma or local anesthetic toxicity. This investigation, however, supports the safety of axillary blockade in patients with preexisting ulnar neuropathy undergoing ulnar nerve transposition.

Suramin-induced neuropathy in an animal model.

Suramin is being used either alone, or in combination with other chemotherapeutic agents, in the treatment of hormone-refractory or metastatic prostate cancer. Use of this potentially valuable chemotherapy is limited by a dose-dependent polyneuropathy. It has been difficult in human studies to characterize peripheral suramin toxicity separately from cancer-related neuropathy. To characterize suramin-induced neuropathy in a rat model, adult rats were given either a single dose of 500 mg/kg (high dose) or 50 mg/kg (low dose) weekly suramin for 2 months. Electrophysiology and peroneal/sural nerve morphometry were performed. In high dose animals, neuropathy developed within 2 weeks, most severe in the digital sensory responses (DSR) (p<0.05) and tail and hind limb compound muscle action potential (p<0.001). Histologically, there was evidence of axonal degeneration and axon atrophy. With low dose suramin, the DSR (p<0.05) and tail distal sensory and motor responses (p<0.01) were most severely affected at 2 months. Axonal degeneration was seen in teased fibers from most animals. With TEM, there were abundant characteristic lysosomal inclusion bodies in DRG and Schwann cells. Electrophysiological and histological evidence of peripheral demyelination was rare, being observed in only one animal. Suramin induced a length, dose and time-dependent axonal sensorimotor polyneuropathy associated with axonal degeneration, atrophy, and accumulation of glycolipid lysosomal inclusions.

Phase III randomized trial of gabapentin in patients with amyotrophic lateral sclerosis.

BACKGROUND: Preclinical and clinical studies of gabapentin in patients with ALS led the authors to undertake a phase III randomized clinical trial. METHODS: Patients were randomly assigned, in a double-blinded fashion, to receive oral gabapentin 3,600 mg or placebo daily for 9 months. The primary outcome measure was the average rate of decline in isometric arm muscle strength for those with two or more evaluations. RESULTS: Two hundred four patients enrolled, 196 had two or more evaluations, and 128 patients completed the study. The mean rate of decline of the arm muscle strength was not significantly different between the groups. Moreover, there was no beneficial effect upon the rate of decline of other secondary measures (vital capacity, survival, ALS functional rating scale, timed walking) nor was there any symptomatic benefit. In fact, analysis of the combined data from the phase II and III trials revealed a significantly more rapid decline of forced vital capacity in patients treated with gabapentin. CONCLUSION: These data provide no evidence of a beneficial effect of gabapentin on disease progression or symptoms in patients with ALS.

Fulminant case of hereditary neuropathy with liability to pressure palsy.

Hereditary neuropathy with liability to pressure palsy (HNPP) is typified as isolated nerve palsies caused by trivial compression or trauma. It rarely presents in two extremities and even more infrequently affects all four limbs simultaneously. We present a patient who concurrently experienced right shoulder, left hand, and bilateral foot weakness mimicking several multifocal conditions. Electromyography suggested HNPP and subsequent nerve biopsy and genetic testing were confirmatory. The case demonstrates that HNPP can present in a fulminant manner and should be included in the differential diagnosis of acute multiple mononeuropathies. The possible causes for such a rapid clinical course in our patient are discussed.

Acute bilateral infarcts of the posterior inferior cerebellar artery.

Acute bilateral infarcts in the territory of the posterior inferior cerebellum artery are rare and poorly documented in the literature. Thus, this report describes the clinical course and outcome in 3 patients. Although one was associated with coronary artery bypass surgery, the etiology was not known. Despite large territorial infarcts, the patients recovered to ambulation with minimal assistance.

Clinical features of perineuritis.

We report 13 patients with pathologically confirmed perineuritis. Seven patients had diabetes mellitus, 5 had nutritional abnormalities, 2 had associated rheumatological illnesses, 2 had sepsis with multiorgan failure, and 1 had a history of malignancy. Electrophysiologic testing demonstrated mononeuritis multiplex in 7, demyelinating neuropathy in 4, distal sensory and motor neuropathy in 1, and polyradiculoneuropathy in 1. Twelve patients received immunomodulating therapy with variable responses. We conclude that perineuritis is associated with a number of different systemic conditions and several clinical patterns of peripheral neuropathy. Response to immunomodulation is variable. The most frequent association is with diabetes mellitus, a previously unrecognized association.

Relative importance of basement membrane and soluble growth factors in delayed and immediate regeneration of rat sciatic nerve.

Sciatic nerve regeneration was studied in two groups of rats. In group I, nerves were transected and transplanted immediately to the contralateral side. In group II, nerves were transected and transplanted 30 days later to the contralateral side. At 4 weeks, group II had an average nerve action potential amplitude of 784 +/- 292 microV and 43.2% +/- 6.7% of myelinated fibers were > 4 microns in diameter. In comparison, the respective measurements were 94 +/- 35.6 microV (p = 0.05) and 29.5% +/- 1.9% (p = 0.04) in group I. At 8 weeks, there were no significant differences in these measurements between groups. These data suggest that the environment in the distal stump improves early regeneration of nerve fibers when that stump was transected 30 days earlier. These and previous findings suggest that soluble trophic factors may be important in initiation of axonal regeneration.