| Ann Neurol. 2009 Apr;65(4):386-93 | ||
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| Therapy 2005 Sep 2 (5):797-805 | ||
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Chronic ischemic monomelic neuropathy from critical limb ischemia. Weinberg DH, Simovic D, Isner J, Ropper AH. Department of Neurology, Tufts University School of Medicine, St. Elizabeth's Medical Center, Boston, MA 02135, USA. David.Weinberg.MD@cchcs.org OBJECTIVE: To describe the peripheral neuropathy resulting from chronic and critical arterial leg ischemia. METHODS: The authors evaluated 19 patients on entry to a gene therapy treatment trial for chronic and critical leg ischemia. Measurements included medical history, examination, neurologic symptom (NSS) and neurologic examination (NES) scores, motor and sensory nerve conduction studies, and quantitative sensory testing. The critically ischemic leg was compared with the less affected contralateral limb. RESULTS: All patients experienced pain from skin ulceration or vascular claudication, but many also had rest pain (58%), numbness (58%), burning (42%), and paresthesias (37%) in the ischemic foot that were consistent with peripheral nerve ischemia. Only three patients (16%) were free of neuropathic symptoms. The most common asymmetric neurologic signs included hypalgesia (74%), toe weakness (64%), hyperesthesia (63%), and pallanesthesia (53%) in the distal leg. NSS and NES were more abnormal in the critically ischemic leg, as were distal motor, total motor, and sensory examination subscores (p < 0.01 for each). Sural sensory potentials were reduced or absent, frequently on both sides. The symptomatic limb had reduced tibial motor amplitudes and increased thermal (cold) sensory thresholds (p < 0.01 for both) whereas the distal latencies, conduction velocities, and vibration thresholds were similar in the two legs. CONCLUSIONS: There is a predominantly sensory neuropathy associated with chronic and critical limb ischemia. Neuropathic symptoms are often obscured by the effects of ischemia on other tissues. The neurophysiologic changes suggest that the underlying pathophysiology is a distal axonopathy affecting nerve fibers of all sizes. Measures of blood flow in the leg correlate with neurologic symptom scores, examination scores, and electrophysiologic testing. PMID: 11571325 [PubMed - indexed for MEDLINE] |
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Improvement in chronic ischemic neuropathy after intramuscular phVEGF165 gene transfer in patients with critical limb ischemia. Simovic D, Isner JM, Ropper AH, Pieczek A, Weinberg DH. St Elizabeth's Medical Center, 736 Cambridge St, Boston, MA 02135, USA. OBJECTIVE: To investigate the effects of vascular endothelial growth factor gene therapy on ischemic neuropathy in patients with critical limb ischemia. DESIGN: An open-label, dose-escalating trial. Patients with angiographically proven critical leg ischemia received injections of phVEGF(165) human plasmid in the muscles of the ischemic limb. Testing before treatment and at 3 and 6 months included (1) symptom severity score, (2) clinical examination score, and (3) electrophysiologic studies. Clinical and electrophysiologic examiners were masked to each other's findings. SETTING: A tertiary care referral hospital and a major teaching affiliate of Tufts University School of Medicine, Boston, Mass. RESULTS: Of 29 consecutive patients enrolled, 17 (19 limbs) completed the 6 months of study. Six patients had diabetes. Compared with baseline studies, treated patients had significant clinical improvements in the symptom score (P<.01), sensory examination score (P<.01), total examination score (P =.01), peroneal motor amplitude (P =.03), and quantitative vibration threshold (P =.04). Improvement in the vascular ankle-brachial index in treated legs (P<.01) corresponded to improvement in neuropathy in the same limb. Neurologic improvement was seen in 4 of 6 patients with diabetes who completed the study. No clinical, electrophysiologic, or vascular improvements were observed in untreated legs. CONCLUSIONS: Ischemic neuropathy might be a reversible condition, and therapeutic angiogenesis might be an effective treatment. The presence of diabetes does not preclude a response to this therapy. PMID: 11346371 [PubMed - indexed for MEDLINE] |
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Carpal tunnel syndrome. Simovic D, Weinberg DH. Division of Neurology, St Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Mass, USA. Carpal tunnel syndrome (CTS) is the most frequently encountered mononeuropathy in the clinical practice. Although now a well recognized entity, it took almost 100 years from the initial observations until the pathophysiology of the disorder was finally accepted as a median nerve compression at the wrist. Sir James Paget (1854)1 was the first to describe the clinical features of CTS. In his first case, a man developed pain and impaired sensation in the hand from the trauma of a cord drawn tightly around his wrist. In his second case, a tardy median nerve palsy was a consequence of a distal radius fracture. This patient improved with wrist immobilization and thus was also the first description of treatment with a neutral wrist splint , a method still in use today. Three decades later James Putnam (1880)2 presented a clinical series of 37 patients with "... disturbances of a subjective sensibility of the skin, giving rise to what is popularly known as numbness recurring periodically, coming on especially at night ... in some cases simply letting the arm hang out of the bed or shaking it about for some moments would drive the numbness away…J.Putnam 1880 “ 2. This vivid description of CTS is quite remarkable considering it was one of the initial clinical observations and that it occurred at the end of the 19th century.
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The median nerve terminal latency index in carpal tunnel syndrome: a clinical case selection study. Simovic D, Weinberg DH. St. Elizabeth's Medical Center, Division of Neurology, Boston, Massachusetts 02135, USA. The terminal latency index (TLI) adjusts the distal motor latency (DL) for the terminal distance and the proximal nerve conduction velocity. We prospectively studied 66 patients in order to assess the sensitivity of the median nerve TLI for the diagnosis of carpal tunnel syndrome (CTS). Clinical and electrophysiological evaluations were completed by separate, blinded examiners. Based on the clinical diagnosis, 54 patients were judged to have CTS (CTS group) and 12 were believed not to have CTS. Control data were obtained from 38 healthy hands. The mean TLI was 0.26 +/- 0.04 in the CTS group and 0.43 +/- 0.04 in the control group (P < 0.001). The sensitivity of the TLI was 81.5%. The TLI was statistically better than the median motor DL and sensory peak latency (PL) to the second digit. The TLI was always abnormal when the median mixed-nerve palmar latency was abnormal. In three cases from the CTS group, the TLI was the only abnormal electrophysiological parameter. The median TLI is a useful, sensitive electrodiagnostic parameter for CTS. Publication Types:
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Comparison of IgM-MGUS and IgG-MGUS polyneuropathy. Simovic D, Gorson KC, Ropper AH. Neurology Service, St Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA 02135, USA. OBJECTIVE: To compare the clinical and electrodiagnostic features and response to treatment in patients with IgM-MGUS and IgG-MGUS associated polyneuropathy. MATERIAL AND METHODS: Retrospective review of 34 consecutive patients with MGUS associated neuropathy evaluated over 5 years. RESULTS: There were 19 patients with IgM-MGUS and 15 with IgG-MGUS. There were no differences in age, duration of symptoms, or distribution of motor and sensory symptoms or signs. IgM-MGUS patients had prolonged distal latencies of the median and ulnar motor potentials, greater slowing of the peroneal nerve conduction velocity and more often absent ulnar sensory potentials. Half of the patients in both groups improved following immunotherapy. CONCLUSION: IgM-MGUS patients had more severe demyelination on the nerve conduction studies, but there were no clinical features that differentiated the 2 groups. IgM and IgG-MGUS patients improved with plasma exchange and other immune therapies. Anti-MAG antibodies failed to distinguish a subgroup of patients with IgM-MGUS neuropathy. PMID: 9531437 [PubMed - indexed for MEDLINE] |
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Terminal latency index in the carpal tunnel syndrome. Simovic D, Weinberg DH. St. Elizabeth's Medical Center, Department of Neurology, Boston, MA 02135, USA. Our retrospective study assessed the validity of the median motor terminal latency index (m-TLI) in evaluation of carpal tunnel syndrome (CTS). In patients deemed most likely to have CTS, the mean m-TLI was markedly reduced at 0.25 while the controls had a mean m-TLI of 0.44. The m-TLI was abnormal in all of the "probable CTS" hands and in none of the control hands. The m-TLI is a sensitive adjunctive electrophysiologic measure for the presence of CTS. PMID: 9270676 [PubMed - indexed for MEDLINE] |
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Improvement following interferon-alpha 2A in chronic inflammatory demyelinating polyneuropathy. Gorson KC, Allam G, Simovic D, Ropper AH. Neurology Service, St. Elizabeth's Medical Center, Boston, MA 02135, USA. Chronic inflammatory demyelinating polyneuropathy (CIDP) is a progressive or relapsing immune-mediated neuropathy usually responsive to plasma exchange, intravenous gammaglobulin or steroids, with some patients being refractory to these conventional therapies. We report a patient with CIDP who had spontaneous improvement after an episode of sepsis, but subsequently relapsed with severe generalized weakness; he was unresponsive to the conventional treatments for CIDP but had dramatic improvement following treatment with interferon-alpha 2A. Nerve conduction studies following treatment showed improved distal compound muscle action potential amplitudes without change in the degree of conduction block. The mechanism of action of interferon-alpha is unknown, but it may modulate proinflammatory cytokines that have a role in immune-mediated demyelination. Interferon-alpha may be an effective alternative therapy in patients with CIDP who relapse or are refractory to conventional treatments. PMID: 9065566 [PubMed - indexed for MEDLINE |
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Treatment of chronic inflammatory demyelinating polyneuropathy with interferon-alpha 2a. Gorson KC, Ropper AH, Clark BD, Dew RB 3rd, Simovic D, Allam G. Division of Neurology, St. Elizabeth's Medical Center, Boston, MA 02135, USA. We performed an open-label, prospective, pilot study of interferon (IFN)-alpha 2a treatment for 6 weeks in 16 patients with chronic inflammatory demyelinating polyneuropathy (CIDP). All patients had failed to improve or relapsed after treatment with at least one conventional therapy (steroids, IV gamma globulin, or plasma exchange). Assessment included MRC strength score, leg sensory score, grip dynanometry, Rankin disability score, electrodiagnostic studies, and serum concentration of tumor necrosis factor-alpha. Nine (56%) improved after IFN-alpha therapy. Mean MRC score increased by 4.2 points (p = 0.01), and mean sensory score improved by 2.3 points (p = 0.02). Five patients improved five or more points on the MRC score, nine had slight improvement or were unchanged, and two worsened. We conclude that IFN-alpha may be effective in some patients with CIDP who relapse or fail to respond to conventional immunomodulating therapy. Publication Types:
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